Pharmacological Basis of Breast Cancer Resistance to Therapies - An Overview

Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]

Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin., 2020, 70(1), 7-30.
[http://dx.doi.org/10.3322/caac.21590] [PMID: 31912902]

Hagemeister, F.B., Jr; Buzdar, A.U.; Luna, M.A.; Blumenschein, G.R. Causes of death in breast cancer: a clinicopathologic study. Cancer, 1980, 46(1), 162-167.
[http://dx.doi.org/10.1002/1097-0142(19800701)46:1<162:AID-CNCR2820460127>3.0.CO;2-B] [PMID: 7388758]

Redig, A.J.; McAllister, S.S. Breast cancer as a systemic disease: a view of metastasis. J. Intern. Med., 2013, 274(2), 113-126.
[http://dx.doi.org/10.1111/joim.12084] [PMID: 23844915]

Gupta, G.P. Massagué, J. Cancer metastasis: building a framework. Cell, 2006, 127(4), 679-695.
[http://dx.doi.org/10.1016/j.cell.2006.11.001] [PMID: 17110329]

Allison, K.H. Molecular pathology of breast cancer: what a pathologist needs to know. Am. J. Clin. Pathol., 2012, 138(6), 770-780.
[http://dx.doi.org/10.1309/AJCPIV9IQ1MRQMOO] [PMID: 23161709]

Steeg, P.S. Targeting metastasis. Nat. Rev. Cancer, 2016, 16(4), 201-218.
[http://dx.doi.org/10.1038/nrc.2016.25] [PMID: 27009393]

Tevaarwerk, A.J.; Gray, R.J.; Schneider, B.P.; Smith, M.L.; Wagner, L.I.; Fetting, J.H.; Davidson, N.; Goldstein, L.J.; Miller, K.D.; Sparano, J.A. Survival in patients with metastatic recurrent breast cancer after adjuvant chemotherapy: little evidence of improvement over the past 30 years. Cancer, 2013, 119(6), 1140-1148.
[http://dx.doi.org/10.1002/cncr.27819] [PMID: 23065954]

Tendl, K.A.; Bago-Horvath, Z. Molecular profiling in breast cancer-ready for clinical routine? Mag. Eur. Med. Oncol., 2020, 13, 445-449.
[http://dx.doi.org/10.1007/s12254-020-00578-0]

Rinaldi, J.; Sokol, E.S.; Hartmaier, R.J.; Trabucco, S.E.; Frampton, G.M.; Goldberg, M.E.; Albacker, L.A.; Daemen, A.; Manning, G. The genomic landscape of metastatic breast cancer: insights from 11,000 tumors. PLoS One, 2020, 15(5),e0231999.
[http://dx.doi.org/10.1371/journal.pone.0231999] [PMID: 32374727]

Curtis, C.; Shah, S.P.; Chin, S.F.; Turashvili, G.; Rueda, O.M.; Dunning, M.J.; Speed, D.; Lynch, A.G.; Samarajiwa, S.; Yuan, Y.; Gräf, S.; Ha, G.; Haffari, G.; Bashashati, A.; Russell, R.; McKinney, S.; Langerød, A.; Green, A.; Provenzano, E.; Wishart, G.; Pinder, S.; Watson, P.; Markowetz, F.; Murphy, L.; Ellis, I.; Purushotham, A.; Børresen-Dale, A.L.; Brenton, J.D.; Tavaré, S.; Caldas, C.; Aparicio, S.; Aparicio, S. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature, 2012, 486(7403), 346-352.
[http://dx.doi.org/10.1038/nature10983] [PMID: 22522925]

Meisel, J.L.; Venur, V.A.; Gnant, M.; Carey, L. evolution of targeted therapy in breast cancer: where precision medicine began. Am. Soc. Clin. Oncol. Educ. Book, 2018, 38, 78-86.
[http://dx.doi.org/10.1200/EDBK_201037] [PMID: 30231395]

Abubakar, M.; Figueroa, J.; Ali, H.R.; Blows, F.; Lissowska, J.; Caldas, C.; Easton, D.F.; Sherman, M.E.; Garcia-Closas, M.; Dowsett, M.; Pharoah, P.D. Combined quantitative measures of ER, PR, HER2, and KI67 provide more prognostic information than categorical combinations in luminal breast cancer. Mod. Pathol., 2019, 32(9), 1244-1256.
[http://dx.doi.org/10.1038/s41379-019-0270-4] [PMID: 30976105]

Perou, C.M.; Sørlie, T.; Eisen, M.B.; van de Rijn, M.; Jeffrey, S.S.; Rees, C.A.; Pollack, J.R.; Ross, D.T.; Johnsen, H.; Akslen, L.A.; Fluge, O.; Pergamenschikov, A.; Williams, C.; Zhu, S.X.; Lønning, P.E.; Børresen-Dale, A.L.; Brown, P.O.; Botstein, D. Molecular portraits of human breast tumours. Nature, 2000, 406(6797), 747-752.
[http://dx.doi.org/10.1038/35021093] [PMID: 10963602]

Cancer Genome Atlas, N. Comprehensive molecular portraits of human breast tumours. Nature, 2012, 490(7418), 61-70.
[http://dx.doi.org/10.1038/nature11412] [PMID: 23000897]

Rozeboom, B.; Dey, N.; De, P.ER. + metastatic breast cancer: past, present, and a prescription for an apoptosis-targeted future. Am. J. Cancer Res., 2019, 9(12), 2821-2831.
[PMID: 31911865]

Smith, I.; Procter, M.; Gelber, R.D.; Guillaume, S.; Feyereislova, A.; Dowsett, M.; Goldhirsch, A.; Untch, M.; Mariani, G.; Baselga, J.; Kaufmann, M.; Cameron, D.; Bell, R.; Bergh, J.; Coleman, R.; Wardley, A.; Harbeck, N.; Lopez, R.I.; Mallmann, P.; Gelmon, K.; Wilcken, N.; Wist, E.; Sánchez Rovira, P.; Piccart-Gebhart, M.J. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet, 2007, 369(9555), 29-36.
[http://dx.doi.org/10.1016/S0140-6736(07)60028-2] [PMID: 17208639]

Romond, E.H.; Perez, E.A.; Bryant, J.; Suman, V.J.; Geyer, C.E., Jr; Davidson, N.E.; Tan-Chiu, E.; Martino, S.; Paik, S.; Kaufman, P.A.; Swain, S.M.; Pisansky, T.M.; Fehrenbacher, L.; Kutteh, L.A.; Vogel, V.G.; Visscher, D.W.; Yothers, G.; Jenkins, R.B.; Brown, A.M.; Dakhil, S.R.; Mamounas, E.P.; Lingle, W.L.; Klein, P.M.; Ingle, J.N.; Wolmark, N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N. Engl. J. Med., 2005, 353(16), 1673-1684.
[http://dx.doi.org/10.1056/NEJMoa052122] [PMID: 16236738]

Swain, S.M.; Baselga, J.; Kim, S.B.; Ro, J.; Semiglazov, V.; Campone, M.; Ciruelos, E.; Ferrero, J.M.; Schneeweiss, A.; Heeson, S.; Clark, E.; Ross, G.; Benyunes, M.C.; Cortés, J.; Group, C.S. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N. Engl. J. Med., 2015, 372(8), 724-734.
[http://dx.doi.org/10.1056/NEJMoa1413513] [PMID: 25693012]

Xuhong, J.C.; Qi, X.W.; Zhang, Y.; Jiang, J. Mechanism, safety and efficacy of three tyrosine kinase inhibitors lapatinib, neratinib and pyrotinib in HER2-positive breast cancer. Am. J. Cancer Res., 2019, 9(10), 2103-2119.
[PMID: 31720077]

Collignon, J.; Lousberg, L.; Schroeder, H.; Jerusalem, G. Triple-negative breast cancer: treatment challenges and solutions. Breast Cancer (Dove Med. Press), 2016, 8, 93-107.
[PMID: 27284266]

Lee, J.M.; Ledermann, J.A.; Kohn, E.C. PARP Inhibitors for BRCA1/2 mutation-associated and BRCA-like malignancies. Ann. Oncol., 2014, 25(1), 32-40.
[http://dx.doi.org/10.1093/annonc/mdt384] [PMID: 24225019]

Gonzalez-Angulo, A.M.; Morales-Vasquez, F.; Hortobagyi, G.N. Overview of resistance to systemic therapy in patients with breast cancer. Adv. Exp. Med. Biol., 2007, 608, 1-22.
[http://dx.doi.org/10.1007/978-0-387-74039-3_1] [PMID: 17993229]

Malmgren, J.; Hurlbert, M.; Atwood, M.; Kaplan, H.G. Examination of a paradox: recurrent metastatic breast cancer incidence decline without improved distant disease survival: 1990-2011. Breast Cancer Res. Treat., 2019, 174(2), 505-514.
[http://dx.doi.org/10.1007/s10549-018-05090-y] [PMID: 30560462]

Higginson, J. Multifactorial carcinogenesis: implications for regulatory practice. Environ. Health Perspect., 1983, 50, 23-26.
[PMID: 6873016]

Hu, Z.; Li, Z.; Ma, Z.; Curtis, C. Multi-cancer analysis of clonality and the timing of systemic spread in paired primary tumors and metastases. Nat. Genet., 2020, 52(7), 701-708.
[http://dx.doi.org/10.1038/s41588-020-0628-z] [PMID: 32424352]

Schubert, M.; Klinger, B.; Klünemann, M.; Sieber, A.; Uhlitz, F.; Sauer, S.; Garnett, M.J.; Blüthgen, N.; Saez-Rodriguez, J. Perturbation-response genes reveal signaling footprints in cancer gene expression. Nat. Commun., 2018, 9(1), 20.
[http://dx.doi.org/10.1038/s41467-017-02391-6] [PMID: 29295995]

Rugo, H.S.; Rumble, R.B.; Macrae, E.; Barton, D.L.; Connolly, H.K.; Dickler, M.N.; Fallowfield, L.; Fowble, B.; Ingle, J.N.; Jahanzeb, M.; Johnston, S.R.; Korde, L.A.; Khatcheressian, J.L.; Mehta, R.S.; Muss, H.B.; Burstein, H.J. Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology Guideline. J. Clin. Oncol., 2016, 34(25), 3069-3103.
[http://dx.doi.org/10.1200/JCO.2016.67.1487] [PMID: 27217461]

Fan, W.; Chang, J.; Fu, P. Endocrine therapy resistance in breast cancer: current status, possible mechanisms and overcoming strategies. Future Med. Chem., 2015, 7(12), 1511-1519.
[http://dx.doi.org/10.4155/fmc.15.93] [PMID: 26306654]

Schiavon, G.; Hrebien, S.; Garcia-Murillas, I.; Cutts, R.J.; Pearson, A.; Tarazona, N.; Fenwick, K.; Kozarewa, I.; Lopez-Knowles, E.; Ribas, R.; Nerurkar, A.; Osin, P.; Chandarlapaty, S.; Martin, L.A.; Dowsett, M.; Smith, I.E.; Turner, N.C. Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer. Sci. Transl. Med., 2015, 7(313),313ra182.
[http://dx.doi.org/10.1126/scitranslmed.aac7551] [PMID: 26560360]

Jeselsohn, R.; Yelensky, R.; Buchwalter, G.; Frampton, G.; Meric-Bernstam, F.; Gonzalez-Angulo, A.M.; Ferrer-Lozano, J.; Perez-Fidalgo, J.A.; Cristofanilli, M.; Gómez, H.; Arteaga, C.L.; Giltnane, J.; Balko, J.M.; Cronin, M.T.; Jarosz, M.; Sun, J.; Hawryluk, M.; Lipson, D.; Otto, G.; Ross, J.S.; Dvir, A.; Soussan-Gutman, L.; Wolf, I.; Rubinek, T.; Gilmore, L.; Schnitt, S.; Come, S.E.; Pusztai, L.; Stephens, P.; Brown, M.; Miller, V.A. Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor-positive breast cancer. Clin. Cancer Res., 2014, 20(7), 1757-1767.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-2332] [PMID: 24398047]

Toy, W.; Shen, Y.; Won, H.; Green, B.; Sakr, R.A.; Will, M.; Li, Z.; Gala, K.; Fanning, S.; King, T.A.; Hudis, C.; Chen, D.; Taran, T.; Hortobagyi, G.; Greene, G.; Berger, M.; Baselga, J.; Chandarlapaty, S. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat. Genet., 2013, 45(12), 1439-1445.
[http://dx.doi.org/10.1038/ng.2822] [PMID: 24185512]

Bidard, F.C.; Callens, C.; Dalenc, F.; Pistilli, B.; Rouge, T.D.L.M.; Clatot, F.; D’hondt, V.; Teixeira, L.; Vegas, H.; Everhard, S.; Lemonnier, J.; Bieche, I.; Pradines, A.; Paitel, J.F.; Spaeth, D.; Moullet, I.; Pierga, J-Y.; Berger, F.; Hardy-Bessard, A-C.; Bachelot, T. Prognostic impact of ESR1 mutations in ER+ HER2- MBC patients prior treated with first line AI and palbociclib: an exploratory analysis of the PADA-1 trial. J. Clin. Oncol., 2020, 38(15)(Suppl.), 1010-1010.
[http://dx.doi.org/10.1200/JCO.2020.38.15_suppl.1010]

Butt, A.J.; McNeil, C.M.; Musgrove, E.A.; Sutherland, R.L. Downstream targets of growth factor and oestrogen signalling and endocrine resistance: the potential roles of c-Myc, cyclin D1 and cyclin E. Endocr. Relat. Cancer, 2005, 12(Suppl. 1), S47-S59.
[http://dx.doi.org/10.1677/erc.1.00993] [PMID: 16113099]

Span, P.N.; Tjan-Heijnen, V.C.; Manders, P.; Beex, L.V.; Sweep, C.G. Cyclin-E is a strong predictor of endocrine therapy failure in human breast cancer. Oncogene, 2003, 22(31), 4898-4904.
[http://dx.doi.org/10.1038/sj.onc.1206818] [PMID: 12894232]

Fox, E.M.; Arteaga, C.L.; Miller, T.W. Abrogating endocrine resistance by targeting ERα and PI3K in breast cancer. Front. Oncol., 2012, 2, 145.
[http://dx.doi.org/10.3389/fonc.2012.00145] [PMID: 23087906]

Yip, C.K.; Murata, K.; Walz, T.; Sabatini, D.M.; Kang, S.A. Structure of the human mTOR complex I and its implications for rapamycin inhibition. Mol. Cell, 2010, 38(5), 768-774.
[http://dx.doi.org/10.1016/j.molcel.2010.05.017] [PMID: 20542007]

Katso, R.; Okkenhaug, K.; Ahmadi, K.; White, S.; Timms, J.; Waterfield, M.D. Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer. Annu. Rev. Cell Dev. Biol., 2001, 17, 615-675.
[http://dx.doi.org/10.1146/annurev.cellbio.17.1.615] [PMID: 11687500]

Yardley, D.A.; Noguchi, S.; Pritchard, K.I.; Burris, H.A., III; Baselga, J.; Gnant, M.; Hortobagyi, G.N.; Campone, M.; Pistilli, B.; Piccart, M.; Melichar, B.; Petrakova, K.; Arena, F.P.; Erdkamp, F.; Harb, W.A.; Feng, W.; Cahana, A.; Taran, T.; Lebwohl, D.; Rugo, H.S. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv. Ther., 2013, 30(10), 870-884.
[http://dx.doi.org/10.1007/s12325-013-0060-1] [PMID: 24158787]

Miller, T.W.; Hennessy, B.T.; González-Angulo, A.M.; Fox, E.M.; Mills, G.B.; Chen, H.; Higham, C.; García-Echeverría, C.; Shyr, Y.; Arteaga, C.L. Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer. J. Clin. Invest., 2010, 120(7), 2406-2413.
[http://dx.doi.org/10.1172/JCI41680] [PMID: 20530877]

Baselga, J.; Campone, M.; Piccart, M.; Burris, H.A., III; Rugo, H.S.; Sahmoud, T.; Noguchi, S.; Gnant, M.; Pritchard, K.I.; Lebrun, F.; Beck, J.T.; Ito, Y.; Yardley, D.; Deleu, I.; Perez, A.; Bachelot, T.; Vittori, L.; Xu, Z.; Mukhopadhyay, P.; Lebwohl, D.; Hortobagyi, G.N. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N. Engl. J. Med., 2012, 366(6), 520-529.
[http://dx.doi.org/10.1056/NEJMoa1109653] [PMID: 22149876]

Bachelot, T.; Bourgier, C.; Cropet, C.; Ray-Coquard, I.; Ferrero, J.M.; Freyer, G.; Abadie-Lacourtoisie, S.; Eymard, J.C.; Debled, M.; Spaëth, D.; Legouffe, E.; Allouache, D.; El Kouri, C.; Pujade-Lauraine, E. Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study. J. Clin. Oncol., 2012, 30(22), 2718-2724.
[http://dx.doi.org/10.1200/JCO.2011.39.0708] [PMID: 22565002]

Piccart, M.; Hortobagyi, G.N.; Campone, M.; Pritchard, K.I.; Lebrun, F.; Ito, Y.; Noguchi, S.; Perez, A.; Rugo, H.S.; Deleu, I.; Burris, H.A., III; Provencher, L.; Neven, P.; Gnant, M.; Shtivelband, M.; Wu, C.; Fan, J.; Feng, W.; Taran, T.; Baselga, J. Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2. Ann. Oncol., 2014, 25(12), 2357-2362.
[http://dx.doi.org/10.1093/annonc/mdu456] [PMID: 25231953]

Serra, V.; Markman, B.; Scaltriti, M.; Eichhorn, P.J.; Valero, V.; Guzman, M.; Botero, M.L.; Llonch, E.; Atzori, F.; Di Cosimo, S.; Maira, M.; Garcia-Echeverria, C.; Parra, J.L.; Arribas, J.; Baselga, J. NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations. Cancer Res., 2008, 68(19), 8022-8030.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-1385] [PMID: 18829560]

Gonzalez-Angulo, A.M.; Blumenschein, G.R., Jr Defining biomarkers to predict sensitivity to PI3K/Akt/mTOR pathway inhibitors in breast cancer. Cancer Treat. Rev., 2013, 39(4), 313-320.
[http://dx.doi.org/10.1016/j.ctrv.2012.11.002] [PMID: 23218708]

Hortobagyi, G.N.; Chen, D.; Piccart, M.; Rugo, H.S.; Burris, H.A., III; Pritchard, K.I.; Campone, M.; Noguchi, S.; Perez, A.T.; Deleu, I.; Shtivelband, M.; Masuda, N.; Dakhil, S.; Anderson, I.; Robinson, D.M.; He, W.; Garg, A.; McDonald, E.R., III; Bitter, H.; Huang, A.; Taran, T.; Bachelot, T.; Lebrun, F.; Lebwohl, D.; Baselga, J. Correlative analysis of genetic alterations and everolimus benefit in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: results from BOLERO-2. J. Clin. Oncol., 2016, 34(5), 419-426.
[http://dx.doi.org/10.1200/JCO.2014.60.1971] [PMID: 26503204]

Treilleux, I.; Arnedos, M.; Cropet, C.; Wang, Q.; Ferrero, J.M.; Abadie-Lacourtoisie, S.; Levy, C.; Legouffe, E.; Lortholary, A.; Pujade-Lauraine, E.; Bourcier, A.V.; Eymard, J.C.; Spaeth, D.; Bachelot, T. Translational studies within the TAMRAD randomized GINECO trial: evidence for mTORC1 activation marker as a predictive factor for everolimus efficacy in advanced breast cancer. Ann. Oncol., 2015, 26(1), 120-125.
[http://dx.doi.org/10.1093/annonc/mdu497] [PMID: 25361980]

Burke, J.E.; Perisic, O.; Masson, G.R.; Vadas, O.; Williams, R.L. Oncogenic mutations mimic and enhance dynamic events in the natural activation of phosphoinositide 3-kinase p110α (PIK3CA). Proc. Natl. Acad. Sci. USA, 2012, 109(38), 15259-15264.
[http://dx.doi.org/10.1073/pnas.1205508109] [PMID: 22949682]

Moynahan, M.E.; Chen, D.; He, W.; Sung, P.; Samoila, A.; You, D.; Bhatt, T.; Patel, P.; Ringeisen, F.; Hortobagyi, G.N.; Baselga, J.; Chandarlapaty, S. Correlation between PIK3CA mutations in cell-free DNA and everolimus efficacy in HR+, HER2- advanced breast cancer: results from BOLERO-2. Br. J. Cancer, 2017, 116(6), 726-730.
[http://dx.doi.org/10.1038/bjc.2017.25] [PMID: 28183140]

Chandarlapaty, S.; Chen, D.; He, W.; Sung, P.; Samoila, A.; You, D.; Bhatt, T.; Patel, P.; Voi, M.; Gnant, M.; Hortobagyi, G.; Baselga, J.; Moynahan, M.E. Prevalence of ESR1 mutations in cell-free DNA and outcomes in metastatic breast cancer: a secondary analysis of the BOLERO-2 clinical trial. JAMA Oncol., 2016, 2(10), 1310-1315.
[http://dx.doi.org/10.1001/jamaoncol.2016.1279] [PMID: 27532364]

Omarini, C.; Filieri, M.E.; Bettelli, S.; Manfredini, S.; Kaleci, S.; Caprera, C.; Nasso, C.; Barbolini, M.; Guaitoli, G.; Moscetti, L.; Maiorana, A.; Conte, P.F.; Cascinu, S.; Piacentini, F. Mutational profile of metastatic breast cancer tissue in patients treated with exemestane plus everolimus. BioMed Res. Int., 2018, 2018,3756981.
[http://dx.doi.org/10.1155/2018/3756981] [PMID: 30140695]

Van den Bossche, V.; Jadot, G.; Grisay, G.; Pierrard, J.; Honoré, N.; Petit, B.; Augusto, D.; Sauvage, S.; Laes, J.F.; Seront, E. c-MET as a potential resistance mechanism to everolimus in breast cancer: from a case report to patient cohort analysis. Target. Oncol., 2020, 15(1), 139-146.
[http://dx.doi.org/10.1007/s11523-020-00704-2] [PMID: 32020516]

Engelman, J.A. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat. Rev. Cancer, 2009, 9(8), 550-562.
[http://dx.doi.org/10.1038/nrc2664] [PMID: 19629070]

Cantley, L.C. The phosphoinositide 3-kinase pathway. Science, 2002, 296(5573), 1655-1657.
[http://dx.doi.org/10.1126/science.296.5573.1655] [PMID: 12040186]

Yang, J.; Nie, J.; Ma, X.; Wei, Y.; Peng, Y.; Wei, X. Targeting PI3K in cancer: mechanisms and advances in clinical trials. Mol. Cancer, 2019, 18(1), 26.
[http://dx.doi.org/10.1186/s12943-019-0954-x] [PMID: 30782187]

Hanker, A.B.; Kaklamani, V.; Arteaga, C.L. Challenges for the clinical development of pi3k inhibitors: strategies to improve their impact in solid tumors. Cancer Discov., 2019, 9(4), 482-491.
[http://dx.doi.org/10.1158/2159-8290.CD-18-1175] [PMID: 30867161]

Vasan, N.; Toska, E.; Scaltriti, M. Overview of the relevance of PI3K pathway in HR-positive breast cancer. Ann. Oncol., 2019, 30(Suppl. 10), x3-x11.
[http://dx.doi.org/10.1093/annonc/mdz281]

Fritsch, C.; Huang, A.; Chatenay-Rivauday, C.; Schnell, C.; Reddy, A.; Liu, M.; Kauffmann, A.; Guthy, D.; Erdmann, D.; De Pover, A.; Furet, P.; Gao, H.; Ferretti, S.; Wang, Y.; Trappe, J.; Brachmann, S.M.; Maira, S.M.; Wilson, C.; Boehm, M.; Garcia-Echeverria, C.; Chene, P.; Wiesmann, M.; Cozens, R.; Lehar, J.; Schlegel, R.; Caravatti, G.; Hofmann, F.; Sellers, W.R. Characterization of the novel and specific PI3Kα inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol. Cancer Ther., 2014, 13(5), 1117-1129.
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0865] [PMID: 24608574]

Juric, D.; Rodon, J.; Tabernero, J.; Janku, F.; Burris, H.A.; Schellens, J.H.M.; Middleton, M.R.; Berlin, J.; Schuler, M.; Gil-Martin, M.; Rugo, H.S.; Seggewiss-Bernhardt, R.; Huang, A.; Bootle, D.; Demanse, D.; Blumenstein, L.; Coughlin, C.; Quadt, C.; Baselga, J. Phosphatidylinositol 3-kinase α-selective inhibition with alpelisib (BYL719) in PIK3CA-altered solid tumors: results from the first-in-human study. J. Clin. Oncol., 2018, 36(13), 1291-1299.
[http://dx.doi.org/10.1200/JCO.2017.72.7107] [PMID: 29401002]

André, F.; Ciruelos, E.; Rubovszky, G.; Campone, M.; Loibl, S.; Rugo, H.S.; Iwata, H.; Conte, P.; Mayer, I.A.; Kaufman, B.; Yamashita, T.; Lu, Y.S.; Inoue, K.; Takahashi, M.; Pápai, Z.; Longin, A.S.; Mills, D.; Wilke, C.; Hirawat, S.; Juric, D. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N. Engl. J. Med., 2019, 380(20), 1929-1940.
[http://dx.doi.org/10.1056/NEJMoa1813904] [PMID: 31091374]

Juric, D.; Ciruelos, E.; Rubovszky, G.; Campone, M.; Loibl, S.; Rugo, H.; Iwata, H.; Conte, P.; Mayer, I.; Kaufman, B.; Yamashita, T.; Lu, Y.-S.; Inoue, K.; Takahashi, M.; Pápai, Z.; Longin, A.-S.; Mills, D.; Wilke, C.; Sellami, D.; Andre, F. . Abstract GS3-08: Alpelisib + fulvestrant for advanced breast cancer: subgroup analyses from the phase III SOLAR-1 trial. Cancer Res., 2019, 79(4 Supplement), GS3-08-GS3-08.

Juric, D.; Castel, P.; Griffith, M.; Griffith, O.L.; Won, H.H.; Ellis, H.; Ebbesen, S.H.; Ainscough, B.J.; Ramu, A.; Iyer, G.; Shah, R.H.; Huynh, T.; Mino-Kenudson, M.; Sgroi, D.; Isakoff, S.; Thabet, A.; Elamine, L.; Solit, D.B.; Lowe, S.W.; Quadt, C.; Peters, M.; Derti, A.; Schegel, R.; Huang, A.; Mardis, E.R.; Berger, M.F.; Baselga, J.; Scaltriti, M. Convergent loss of PTEN leads to clinical resistance to a PI(3)Kα inhibitor. Nature, 2015, 518(7538), 240-244.
[http://dx.doi.org/10.1038/nature13948] [PMID: 25409150]

Jia, S.; Liu, Z.; Zhang, S.; Liu, P.; Zhang, L.; Lee, S.H.; Zhang, J.; Signoretti, S.; Loda, M.; Roberts, T.M.; Zhao, J.J. Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis. Nature, 2008, 454(7205), 776-779.
[http://dx.doi.org/10.1038/nature07091] [PMID: 18594509]

Wee, S.; Wiederschain, D.; Maira, S.M.; Loo, A.; Miller, C.; deBeaumont, R.; Stegmeier, F.; Yao, Y.M.; Lengauer, C. PTEN-deficient cancers depend on PIK3CB. Proc. Natl. Acad. Sci. USA, 2008, 105(35), 13057-13062.
[http://dx.doi.org/10.1073/pnas.0802655105] [PMID: 18755892]

Schmid, P.; Pinder, S.E.; Wheatley, D.; Macaskill, J.; Zammit, C.; Hu, J.; Price, R.; Bundred, N.; Hadad, S.; Shia, A.; Sarker, S.J.; Lim, L.; Gazinska, P.; Woodman, N.; Korbie, D.; Trau, M.; Mainwaring, P.; Gendreau, S.; Lackner, M.R.; Derynck, M.; Wilson, T.R.; Butler, H.; Earl, G.; Parker, P.; Purushotham, A.; Thompson, A. Phase II randomized preoperative window-of-opportunity study of the PI3K inhibitor pictilisib plus anastrozole compared with anastrozole alone in patients with estrogen receptor-positive breast cancer. J. Clin. Oncol., 2016, 34(17), 1987-1994.
[http://dx.doi.org/10.1200/JCO.2015.63.9179] [PMID: 26976426]

Schmid, P.; Pinder, S.; Wheatley, D.; Zummit, C.; Macaskill, E.; Hu, J.; Price, R.; Bundred, N.; Hadad, S.; Shia, A.; Sarker, S.-J.; Lim, L.; Mousa, K.; O'Brien, C.; Wilson, T.; Lackner, M.; Gendreau, S.; Gazinska, P.; Korbie, D.; Trau, M.; Mainwaring, P.; Thompson, A.; Purushotham, A. Abstract P2-08-02: Interaction of PIK3CA mutation subclasses with response to preoperative treatment with the PI3K inhibitor pictilisib in patients with estrogen receptor-positive breast cancer. Cancer Res.,, 2019, 79(4 Supplement), P2-08-02-P2-08-02.

Mayer, I.A.; Abramson, V.G.; Formisano, L.; Balko, J.M.; Estrada, M.V.; Sanders, M.E.; Juric, D.; Solit, D.; Berger, M.F.; Won, H.H.; Li, Y.; Cantley, L.C.; Winer, E.; Arteaga, C.L. A Phase Ib study of alpelisib (BYL719), a PI3Kα-specific inhibitor, with letrozole in ER+/HER2- metastatic breast cancer. Clin. Cancer Res., 2017, 23(1), 26-34.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-0134] [PMID: 27126994]

Mosele, F.; Stefanovska, B.; Lusque, A.; Tran Dien, A.; Garberis, I.; Droin, N.; Le Tourneau, C.; Sablin, M.P.; Lacroix, L.; Enrico, D.; Miran, I.; Jovelet, C.; Bièche, I.; Soria, J.C.; Bertucci, F.; Bonnefoi, H.; Campone, M.; Dalenc, F.; Bachelot, T.; Jacquet, A.; Jimenez, M.; André, F. Outcome and molecular landscape of patients with PIK3CA-mutated metastatic breast cancer. Ann. Oncol., 2020, 31(3), 377-386.
[http://dx.doi.org/10.1016/j.annonc.2019.11.006] [PMID: 32067679]

Avivar-Valderas, A.; McEwen, R.; Taheri-Ghahfarokhi, A.; Carnevalli, L.S.; Hardaker, E.L.; Maresca, M.; Hudson, K.; Harrington, E.A.; Cruzalegui, F. Functional significance of co-occurring mutations in PIK3CA and MAP3K1 in breast cancer. Oncotarget, 2018, 9(30), 21444-21458.
[http://dx.doi.org/10.18632/oncotarget.25118] [PMID: 29765551]

Herrera-Abreu, M.T.; Palafox, M.; Asghar, U.; Rivas, M.A.; Cutts, R.J.; Garcia-Murillas, I.; Pearson, A.; Guzman, M.; Rodriguez, O.; Grueso, J.; Bellet, M.; Cortés, J.; Elliott, R.; Pancholi, S.; Baselga, J.; Dowsett, M.; Martin, L.A.; Turner, N.C.; Serra, V. Early adaptation and acquired resistance to CDK4/6 inhibition in estrogen receptor-positive breast cancer. Cancer Res., 2016, 76(8), 2301-2313.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-0728] [PMID: 27020857]

Available from. https://clinicaltrials.gov/ct2/show/study/NCT02088684

Hoffmann, J.; Bohlmann, R.; Heinrich, N.; Hofmeister, H.; Kroll, J.; Künzer, H.; Lichtner, R.B.; Nishino, Y.; Parczyk, K.; Sauer, G.; Gieschen, H.; Ulbrich, H.F.; Schneider, M.R. Characterization of new estrogen receptor destabilizing compounds: effects on estrogen-sensitive and tamoxifen-resistant breast cancer. J. Natl. Cancer Inst., 2004, 96(3), 210-218.
[http://dx.doi.org/10.1093/jnci/djh022] [PMID: 14759988]

Osborne, C.K.; Schiff, R. Mechanisms of endocrine resistance in breast cancer. Annu. Rev. Med., 2011, 62, 233-247.
[http://dx.doi.org/10.1146/annurev-med-070909-182917] [PMID: 20887199]

Vogelstein, B.; Papadopoulos, N.; Velculescu, V.E.; Zhou, S.; Diaz, L.A., Jr; Kinzler, K.W. Cancer genome landscapes. Science, 2013, 339(6127), 1546-1558.
[http://dx.doi.org/10.1126/science.1235122] [PMID: 23539594]

O’Leary, B.; Finn, R.S.; Turner, N.C. Treating cancer with selective CDK4/6 inhibitors. Nat. Rev. Clin. Oncol., 2016, 13(7), 417-430.
[http://dx.doi.org/10.1038/nrclinonc.2016.26] [PMID: 27030077]

Finn, R.S.; Crown, J.P.; Lang, I.; Boer, K.; Bondarenko, I.M.; Kulyk, S.O.; Ettl, J.; Patel, R.; Pinter, T.; Schmidt, M.; Shparyk, Y.; Thummala, A.R.; Voytko, N.L.; Fowst, C.; Huang, X.; Kim, S.T.; Randolph, S.; Slamon, D.J. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol., 2015, 16(1), 25-35.
[http://dx.doi.org/10.1016/S1470-2045(14)71159-3] [PMID: 25524798]

Rascon, K.; Flajc, G.; De Angelis, C.; Liu, X.; Trivedi, M.V.; Ekinci, E. Ribociclib in HR+/HER2- advanced or metastatic breast cancer patients. Ann. Pharmacother., 2019, 53(5), 501-509.
[http://dx.doi.org/10.1177/1060028018817904] [PMID: 30522347]

Grischke, E.M.; Neven, P.; Lin, Y.; Kaufman, P.A.; Sledge, G.W. Abemaciclib with fulvestrant in patients with HR+, HER2- Advanced Breast Cance (ABC) that exhibited primary or secondary resistance to prior Endocrin Therapy (ET). Ann. Oncol., 2018, 29, viii106.

Condorelli, R.; Spring, L.; O’Shaughnessy, J.; Lacroix, L.; Bailleux, C.; Scott, V.; Dubois, J.; Nagy, R.J.; Lanman, R.B.; Iafrate, A.J.; Andre, F.; Bardia, A. Polyclonal RB1 mutations and acquired resistance to CDK 4/6 inhibitors in patients with metastatic breast cancer. Ann. Oncol., 2018, 29(3), 640-645.
[http://dx.doi.org/10.1093/annonc/mdx784] [PMID: 29236940]

Malorni, L.; Piazza, S.; Ciani, Y.; Guarducci, C.; Bonechi, M.; Biagioni, C.; Hart, C.D.; Verardo, R.; Di Leo, A.; Migliaccio, I. A gene expression signature of retinoblastoma loss-of-function is a predictive biomarker of resistance to palbociclib in breast cancer cell lines and is prognostic in patients with ER positive early breast cancer. Oncotarget, 2016, 7(42), 68012-68022.
[http://dx.doi.org/10.18632/oncotarget.12010] [PMID: 27634906]

Turner, N.C.; O’Leary, B.; Cutts, R.; Liu, Y.; Hrebien, S.; Huang, X.; Beaney, M.; Fenwick, K.; Andre, F.; Loibl, S.; Loi, S.; Garcia-Murillas, I.; Bartlett, C.H.; Cristofanilli, M. Genetic landscape of resistance to CDK4/6 inhibition in circulating tumor DNA (ctDNA) analysis of the PALOMA3 trial of palbociclib and fulvestrant versus placebo and fulvestrant. J. Clin. Oncol., 2018, 36(15)(Suppl.), 1001-1001.
[http://dx.doi.org/10.1200/JCO.2018.36.15_suppl.1001]

O’Leary, B.; Cutts, R.J.; Liu, Y.; Hrebien, S.; Huang, X.; Fenwick, K.; André, F.; Loibl, S.; Loi, S.; Garcia-Murillas, I.; Cristofanilli, M.; Huang Bartlett, C.; Turner, N.C. The genetic landscape and clonal evolution of breast cancer resistance to palbociclib plus fulvestrant in the PALOMA-3 trial. Cancer Discov., 2018, 8(11), 1390-1403.
[http://dx.doi.org/10.1158/2159-8290.CD-18-0264] [PMID: 30206110]

Wander, S.A.; Cohen, O.; Gong, X.; Johnson, G.N.; Buendia-Buendia, J.E.; Lloyd, M.R.; Kim, D.; Luo, F.; Mao, P.; Helvie, K.; Kowalski, K.J.; Nayar, U.; Waks, A.G.; Parsons, S.H.; Martinez, R.; Litchfield, L.M.; Ye, X.S.; Yu, C.; Jansen, V.M.; Stille, J.R.; Smith, P.S.; Oakley, G.J.; Chu, Q.S.; Batist, G.; Hughes, M.E.; Kremer, J.D.; Garraway, L.A.; Winer, E.P.; Tolaney, S.M.; Lin, N.U.; Buchanan, S.G.; Wagle, N. The genomic landscape of intrinsic and acquired resistance to cyclin-dependent kinase 4/6 inhibitors in patients with hormone receptor-positive metastatic breast cancer. Cancer Discov., 2020, 10(8), 1174-1193.
[http://dx.doi.org/10.1158/2159-8290.CD-19-1390] [PMID: 32404308]

Pancholi, S.; Ribas, R.; Simigdala, N.; Schuster, E.; Nikitorowicz-Buniak, J.; Ressa, A.; Gao, Q.; Leal, M.F.; Bhamra, A.; Thornhill, A.; Morisset, L.; Montaudon, E.; Sourd, L.; Fitzpatrick, M.; Altelaar, M.; Johnston, S.R.; Marangoni, E.; Dowsett, M.; Martin, L.A. Tumour kinome re-wiring governs resistance to palbociclib in oestrogen receptor positive breast cancers, highlighting new therapeutic modalities. Oncogene, 2020, 39(25), 4781-4797.
[http://dx.doi.org/10.1038/s41388-020-1284-6] [PMID: 32307447]

Yang, C.; Li, Z.; Bhatt, T.; Dickler, M.; Giri, D.; Scaltriti, M.; Baselga, J.; Rosen, N.; Chandarlapaty, S. Acquired CDK6 amplification promotes breast cancer resistance to CDK4/6 inhibitors and loss of ER signaling and dependence. Oncogene, 2017, 36(16), 2255-2264.
[http://dx.doi.org/10.1038/onc.2016.379] [PMID: 27748766]

Iida, M.; Toyosawa, D.; Nakamura, M.; Tsuboi, K.; Tokuda, E.; Niwa, T.; Ishida, T.; Hayashi, S.I. Decreased ER dependency after acquired resistance to CDK4/6 inhibitors. Breast Cancer, 2020, 27(5), 963-972.
[http://dx.doi.org/10.1007/s12282-020-01090-3] [PMID: 32297248]

Caligiuri, I.; Toffoli, G.; Giordano, A.; Rizzolio, F. pRb controls estrogen receptor alpha protein stability and activity. Oncotarget, 2013, 4(6), 875-883.
[http://dx.doi.org/10.18632/oncotarget.1036] [PMID: 23900261]

Bertoli, C.; Skotheim, J.M.; de Bruin, R.A. Control of cell cycle transcription during G1 and S phases. Nat. Rev. Mol. Cell Biol., 2013, 14(8), 518-528.
[http://dx.doi.org/10.1038/nrm3629] [PMID: 23877564]

Donjerkovic, D.; Scott, D.W. Regulation of the G1 phase of the mammalian cell cycle. Cell Res., 2000, 10(1), 1-16.
[http://dx.doi.org/10.1038/sj.cr.7290031] [PMID: 10765979]

Dean, J.L.; Thangavel, C.; McClendon, A.K.; Reed, C.A.; Knudsen, E.S. Therapeutic CDK4/6 inhibition in breast cancer: key mechanisms of response and failure. Oncogene, 2010, 29(28), 4018-4032.
[http://dx.doi.org/10.1038/onc.2010.154] [PMID: 20473330]

Turner, N.C.; Liu, Y.; Zhu, Z.; Loi, S.; Colleoni, M.; Loibl, S.; DeMichele, A.; Harbeck, N.; André, F.; Bayar, M.A.; Michiels, S.; Zhang, Z.; Giorgetti, C.; Arnedos, M.; Huang Bartlett, C.; Cristofanilli, M. Cyclin E1 expression and palbociclib efficacy in previously treated hormone receptor-positive metastatic breast cancer. J. Clin. Oncol., 2019, 37(14), 1169-1178.
[http://dx.doi.org/10.1200/JCO.18.00925] [PMID: 30807234]

Pandey, K.; An, H.J.; Kim, S.K.; Lee, S.A.; Kim, S.; Lim, S.M.; Kim, G.M.; Sohn, J.; Moon, Y.W. Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer: a review. Int. J. Cancer, 2019, 145(5), 1179-1188.
[http://dx.doi.org/10.1002/ijc.32020] [PMID: 30478914]

Del Re, M.; Bertolini, I.; Crucitta, S.; Fontanelli, L.; Rofi, E.; De Angelis, C.; Diodati, L.; Cavallero, D.; Gianfilippo, G.; Salvadori, B.; Fogli, S.; Falcone, A.; Scatena, C.; Naccarato, A.G.; Roncella, M.; Ghilli, M.; Morganti, R.; Fontana, A.; Danesi, R. Overexpression of TK1 and CDK9 in plasma-derived exosomes is associated with clinical resistance to CDK4/6 inhibitors in metastatic breast cancer patients. Breast Cancer Res. Treat., 2019, 178(1), 57-62.
[http://dx.doi.org/10.1007/s10549-019-05365-y] [PMID: 31346846]

Li, Z.; Razavi, P.; Li, Q.; Toy, W.; Liu, B.; Ping, C.; Hsieh, W.; Sanchez-Vega, F.; Brown, D.N.; Da Cruz Paula, A.F.; Morris, L.; Selenica, P.; Eichenberger, E.; Shen, R.; Schultz, N.; Rosen, N.; Scaltriti, M.; Brogi, E.; Baselga, J.; Reis-Filho, J.S.; Chandarlapaty, S. Loss of the FAT1 Tumor suppressor promotes resistance to CDK4/6 inhibitors via the hippo pathway. Cancer Cell, 2018, 34(6), 893-905.
[http://dx.doi.org/10.1016/j.ccell.2018.11.006] [PMID: 30537512]

Formisano, L.; Lu, Y.; Servetto, A.; Hanker, A.B.; Jansen, V.M.; Bauer, J.A.; Sudhan, D.R.; Guerrero-Zotano, A.L.; Croessmann, S.; Guo, Y.; Ericsson, P.G.; Lee, K.M.; Nixon, M.J.; Schwarz, L.J.; Sanders, M.E.; Dugger, T.C.; Cruz, M.R.; Behdad, A.; Cristofanilli, M.; Bardia, A.; O’Shaughnessy, J.; Nagy, R.J.; Lanman, R.B.; Solovieff, N.; He, W.; Miller, M.; Su, F.; Shyr, Y.; Mayer, I.A.; Balko, J.M.; Arteaga, C.L. Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer. Nat. Commun., 2019, 10(1), 1373.
[http://dx.doi.org/10.1038/s41467-019-09068-2] [PMID: 30914635]

Costa, C.; Wang, Y.; Ly, A.; Hosono, Y.; Murchie, E.; Walmsley, C.S.; Huynh, T.; Healy, C.; Peterson, R.; Yanase, S.; Jakubik, C.T.; Henderson, L.E.; Damon, L.J.; Timonina, D.; Sanidas, I.; Pinto, C.J.; Mino-Kenudson, M.; Stone, J.R.; Dyson, N.J.; Ellisen, L.W.; Bardia, A.; Ebi, H.; Benes, C.H.; Engelman, J.A.; Juric, D. PTEN loss mediates clinical cross-resistance to CDK4/6 and PI3Kα inhibitors in breast cancer. Cancer Discov., 2020, 10(1), 72-85.
[http://dx.doi.org/10.1158/2159-8290.CD-18-0830] [PMID: 31594766]

Del Re, M.; Crucitta, S.; Lorenzini, G.; De Angelis, C.; Diodati, L.; Cavallero, D.; Bargagna, I.; Cinacchi, P.; Fratini, B.; Salvadori, B.; Ghilli, M.; Roncella, M.; Fontana, A.; Danesi, R.; Cucchiara, F. PI3K mutations detected in liquid biopsy are associated to reduced sensitivity to CDK4/6 inhibitors in metastatic breast cancer patients. Pharmacol. Res., 2021, 163,105241.
[http://dx.doi.org/10.1016/j.phrs.2020.105241] [PMID: 33049397]

Portman, N.; Milioli, H.H.; Alexandrou, S.; Coulson, R.; Yong, A.; Fernandez, K.J.; Chia, K.M.; Halilovic, E.; Segara, D.; Parker, A.; Haupt, S.; Haupt, Y.; Tilley, W.D.; Swarbrick, A.; Caldon, C.E.; Lim, E. MDM2 inhibition in combination with endocrine therapy and CDK4/6 inhibition for the treatment of ER-positive breast cancer. Breast Cancer Res., 2020, 22(1), 87.
[http://dx.doi.org/10.1186/s13058-020-01318-2] [PMID: 32787886]

Slamon, D.J.; Clark, G.M.; Wong, S.G.; Levin, W.J.; Ullrich, A.; McGuire, W.L. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science, 1987, 235(4785), 177-182.
[http://dx.doi.org/10.1126/science.3798106] [PMID: 3798106]

Mezni, E.; Vicier, C.; Guerin, M.; Sabatier, R.; Bertucci, F.; Gonçalves, A. New therapeutics in HER2-positive advanced breast cancer: towards a change in clinical practices. Cancers (Basel), 2020, 12(6),E1573.
[http://dx.doi.org/10.3390/cancers12061573] [PMID: 32545895]

Moasser, M.M. The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene, 2007, 26(45), 6469-6487.
[http://dx.doi.org/10.1038/sj.onc.1210477] [PMID: 17471238]

Browne, B.C.; O’Brien, N.; Duffy, M.J.; Crown, J.; O’Donovan, N. HER-2 signaling and inhibition in breast cancer. Curr. Cancer Drug Targets, 2009, 9(3), 419-438.
[http://dx.doi.org/10.2174/156800909788166484] [PMID: 19442060]

Lee-Hoeflich, S.T.; Crocker, L.; Yao, E.; Pham, T.; Munroe, X.; Hoeflich, K.P.; Sliwkowski, M.X.; Stern, H.M. A central role for HER3 in HER2-amplified breast cancer: implications for targeted therapy. Cancer Res., 2008, 68(14), 5878-5887.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-0380] [PMID: 18632642]

Wang, Z.; Erb, B. Receptors and Cancer. Methods Mol. Biol., 2017, 1652, 3-35.
[http://dx.doi.org/10.1007/978-1-4939-7219-7_1] [PMID: 28791631]

Le, X.F.; Pruefer, F.; Bast, R.C., Jr HER2-targeting antibodies modulate the cyclin-dependent kinase inhibitor p27Kip1 via multiple signaling pathways. Cell Cycle, 2005, 4(1), 87-95.
[http://dx.doi.org/10.4161/cc.4.1.1360] [PMID: 15611642]

Stern, H.M. Improving treatment of HER2-positive cancers: opportunities and challenges. Sci. Transl. Med., 2012, 4(127),127rv2.
[http://dx.doi.org/10.1126/scitranslmed.3001539] [PMID: 22461643]

Franklin, M.C.; Carey, K.D.; Vajdos, F.F.; Leahy, D.J.; de Vos, A.M.; Sliwkowski, M.X. Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell, 2004, 5(4), 317-328.
[http://dx.doi.org/10.1016/S1535-6108(04)00083-2] [PMID: 15093539]

Carter, P.; Presta, L.; Gorman, C.M.; Ridgway, J.B.; Henner, D.; Wong, W.L.; Rowland, A.M.; Kotts, C.; Carver, M.E.; Shepard, H.M. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc. Natl. Acad. Sci. USA, 1992, 89(10), 4285-4289.
[http://dx.doi.org/10.1073/pnas.89.10.4285] [PMID: 1350088]

Siegel, J.P. Herceptin FDA approval letter., Available from: https://www.accessdata.fda.gov/drugsatfda_docs/appletter/1998/trasgen092598L.pdf

Cuello, M.; Ettenberg, S.A.; Clark, A.S.; Keane, M.M.; Posner, R.H.; Nau, M.M.; Dennis, P.A.; Lipkowitz, S. Down-regulation of the erbB-2 receptor by trastuzumab (herceptin) enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in breast and ovarian cancer cell lines that overexpress ErbB-2. Cancer Res., 2001, 61(12), 4892-4900.
[PMID: 11406568]

Junttila, T.T.; Akita, R.W.; Parsons, K.; Fields, C.; Lewis Phillips, G.D.; Friedman, L.S.; Sampath, D.; Sliwkowski, M.X. Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell, 2009, 15(5), 429-440.
[http://dx.doi.org/10.1016/j.ccr.2009.03.020] [PMID: 19411071]

Collins, D.M.; O’Donovan, N.; McGowan, P.M.; O’Sullivan, F.; Duffy, M.J.; Crown, J. Trastuzumab induces Antibody-Dependent Cell-mediated Cytotoxicity (ADCC) in HER-2-non-amplified breast cancer cell lines. Ann. Oncol., 2012, 23(7), 1788-1795.
[http://dx.doi.org/10.1093/annonc/mdr484] [PMID: 22056974]

Petricevic, B.; Laengle, J.; Singer, J.; Sachet, M.; Fazekas, J.; Steger, G.; Bartsch, R.; Jensen-Jarolim, E.; Bergmann, M. Trastuzumab mediates antibody-dependent cell-mediated cytotoxicity and phagocytosis to the same extent in both adjuvant and metastatic HER2/neu breast cancer patients. J. Transl. Med., 2013, 11, 307.
[http://dx.doi.org/10.1186/1479-5876-11-307] [PMID: 24330813]

Zhang, A.; Shen, G.; Zhao, T.; Zhang, G.; Liu, J.; Song, L.; Wei, W.; Bing, L.; Wu, Z.; Wu, Q. Augmented inhibition of angiogenesis by combination of HER2 antibody chA21 and trastuzumab in human ovarian carcinoma xenograft. J. Ovarian Res., 2010, 3, 20.
[http://dx.doi.org/10.1186/1757-2215-3-20] [PMID: 20723224]

Wang, C.; Wang, L.; Yu, X.; Zhang, Y.; Meng, Y.; Wang, H.; Yang, Y.; Gao, J.; Wei, H.; Zhao, J.; Lu, C.; Chen, H.; Sun, Y.; Li, B. Combating acquired resistance to trastuzumab by an anti-ErbB2 fully human antibody. Oncotarget, 2017, 8(26), 42742-42751.
[http://dx.doi.org/10.18632/oncotarget.17451] [PMID: 28514745]

Ozkavruk Eliyatkin, N.; Aktas, S.; Ozgur, H.; Ercetin, P.; Kupelioglu, A. The role of p95HER2 in trastuzumab resistance in breast cancer. J. BUON, 2016, 21(2), 382-389.
[PMID: 27273948]

Vu, T.; Claret, F.X. Trastuzumab: updated mechanisms of action and resistance in breast cancer. Front. Oncol., 2012, 2, 62.
[http://dx.doi.org/10.3389/fonc.2012.00062] [PMID: 22720269]

Maximiano, S.; Magalhães, P.; Guerreiro, M.P.; Morgado, M. Trastuzumab in the treatment of breast cancer. BioDrugs, 2016, 30(2), 75-86.
[http://dx.doi.org/10.1007/s40259-016-0162-9] [PMID: 26892619]

Lu, Y.; Zi, X.; Zhao, Y.; Mascarenhas, D.; Pollak, M. Insulin-like growth factor-I receptor signaling and resistance to trastuzumab (Herceptin). J. Natl. Cancer Inst., 2001, 93(24), 1852-1857.
[http://dx.doi.org/10.1093/jnci/93.24.1852] [PMID: 11752009]

Shattuck, D.L.; Miller, J.K.; Carraway, K.L., III; Sweeney, C. Met receptor contributes to trastuzumab resistance of Her2-overexpressing breast cancer cells. Cancer Res., 2008, 68(5), 1471-1477.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-5962] [PMID: 18316611]

Wang, L.; Zhang, Q.; Zhang, J.; Sun, S.; Guo, H.; Jia, Z.; Wang, B.; Shao, Z.; Wang, Z.; Hu, X. PI3K pathway activation results in low efficacy of both trastuzumab and lapatinib. BMC Cancer, 2011, 11, 248.
[http://dx.doi.org/10.1186/1471-2407-11-248] [PMID: 21676217]

Nagata, Y.; Lan, K.H.; Zhou, X.; Tan, M.; Esteva, F.J.; Sahin, A.A.; Klos, K.S.; Li, P.; Monia, B.P.; Nguyen, N.T.; Hortobagyi, G.N.; Hung, M.C.; Yu, D. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell, 2004, 6(2), 117-127.
[http://dx.doi.org/10.1016/j.ccr.2004.06.022] [PMID: 15324695]

Scheuer, W.; Friess, T.; Burtscher, H.; Bossenmaier, B.; Endl, J.; Hasmann, M. Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res., 2009, 69(24), 9330-9336.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-4597] [PMID: 19934333]

Cortés, J.; Baselga, J.; Petrella, T.; Gelmon, K.; Fumoleau, P.; Verma, S.; Pivot, X.; Ross, G.; Szado, T.; Gianni, L. Pertuzumab monotherapy following trastuzumab-based treatment: activity and tolerability in patients with advanced HER2- positive breast cancer. J. Clin. Oncol., 2009, 27(15)(Suppl.), 1022-1022.
[http://dx.doi.org/10.1200/jco.2009.27.15_suppl.1022]

Hutcheson, I.; Barrow, D.; Hasmann, M.; Nicholson, R. Induction of erbB3/EGFR heterodimers mediates resistance to pertuzumab in a tamoxifen-resistant MCF-7 breast cancer cell line. Mol. Cancer Ther., 2007, 6(11)(Suppl.), A118-A118.

Verma, S.; Miles, D.; Gianni, L.; Krop, I.E.; Welslau, M.; Baselga, J.; Pegram, M.; Oh, D.Y.; Diéras, V.; Guardino, E.; Fang, L.; Lu, M.W.; Olsen, S.; Blackwell, K.; Group, E.S. Trastuzumab emtansine for HER2-positive advanced breast cancer. N. Engl. J. Med., 2012, 367(19), 1783-1791.
[http://dx.doi.org/10.1056/NEJMoa1209124] [PMID: 23020162]

Hunter, F.W.; Barker, H.R.; Lipert, B.; Rothé, F.; Gebhart, G.; Piccart-Gebhart, M.J.; Sotiriou, C.; Jamieson, S.M.F. Mechanisms of resistance to trastuzumab emtansine (T-DM1) in HER2-positive breast cancer. Br. J. Cancer, 2020, 122(5), 603-612.
[http://dx.doi.org/10.1038/s41416-019-0635-y] [PMID: 31839676]

Lewis Phillips, G.D.; Li, G.; Dugger, D.L.; Crocker, L.M.; Parsons, K.L.; Mai, E.; Blättler, W.A.; Lambert, J.M.; Chari, R.V.; Lutz, R.J.; Wong, W.L.; Jacobson, F.S.; Koeppen, H.; Schwall, R.H.; Kenkare-Mitra, S.R.; Spencer, S.D.; Sliwkowski, M.X. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res., 2008, 68(22), 9280-9290.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-1776] [PMID: 19010901]

Filho, O.M.; Viale, G.; Trippa, L.; Li, T.; Yardley, D.A.; Mayer, I.A.; Abramson, V.G.; Arteaga, C.L.; Spring, L.; Waks, A.G.; Janiszewska, M.; Wrabel, E.; Demeo, M.; Bardia, A.; King, T.A.; Polyak, K.; Winer, E.P.; Krop, I.E. HER2 heterogeneity as a predictor of response to neoadjuvant T-DM1 plus pertuzumab: results from a prospective clinical trial. J. Clin. Oncol., 2019, 37(15)(Suppl.), 502-502.
[http://dx.doi.org/10.1200/JCO.2019.37.15_suppl.502]

Mercogliano, M.F.; De Martino, M.; Venturutti, L.; Rivas, M.A.; Proietti, C.J.; Inurrigarro, G.; Frahm, I.; Allemand, D.H.; Deza, E.G.; Ares, S.; Gercovich, F.G.; Guzmán, P.; Roa, J.C.; Elizalde, P.V.; Schillaci, R. TNFα-induced mucin 4 expression elicits trastuzumab resistance in HER2-positive breast cancer. Clin. Cancer Res., 2017, 23(3), 636-648.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-0970] [PMID: 27698002]

García-Alonso, S.; Ocaña, A.; Pandiella, A. Trastuzumab emtansine: mechanisms of action and resistance, clinical progress, and beyond. Trends Cancer, 2020, 6(2), 130-146.
[http://dx.doi.org/10.1016/j.trecan.2019.12.010] [PMID: 32061303]

Sauveur, J.; Conilh, L.; Beaumel, S.; Chettab, K.; Jordheim, L.P.; Matera, E.L.; Dumontet, C. Characterization of T-DM1-resistant breast cancer cells. Pharmacol. Res. Perspect., 2020, 8(4),e00617.
[http://dx.doi.org/10.1002/prp2.617] [PMID: 32583565]

Hamblett, K.J.; Jacob, A.P.; Gurgel, J.L.; Tometsko, M.E.; Rock, B.M.; Patel, S.K.; Milburn, R.R.; Siu, S.; Ragan, S.P.; Rock, D.A.; Borths, C.J.; O’Neill, J.W.; Chang, W.S.; Weidner, M.F.; Bio, M.M.; Quon, K.C.; Fanslow, W.C. SLC46A3 is required to transport catabolites of noncleavable antibody maytansine conjugates from the lysosome to the cytoplasm. Cancer Res., 2015, 75(24), 5329-5340.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-1610] [PMID: 26631267]

Saatci, Ö.; Borgoni, S.; Akbulut, Ö.; Durmuş, S.; Raza, U.; Eyüpoğlu, E.; Alkan, C.; Akyol, A.; Kütük, Ö.; Wiemann, S.; Şahin, Ö. Targeting PLK1 overcomes T-DM1 resistance via CDK1-dependent phosphorylation and inactivation of Bcl-2/xL in HER2-positive breast cancer. Oncogene, 2018, 37(17), 2251-2269.
[http://dx.doi.org/10.1038/s41388-017-0108-9] [PMID: 29391599]

Gandalovičová, A.; Rosel, D.; Fernandes, M.; Veselý, P.; Heneberg, P.; Čermák, V.; Petruželka, L.; Kumar, S.; Sanz-Moreno, V.; Brábek, J. Migrastatics-anti-metastatic and anti-invasion drugs: promises and challenges. Trends Cancer, 2017, 3(6), 391-406.
[http://dx.doi.org/10.1016/j.trecan.2017.04.008] [PMID: 28670628]

Tevaarwerk, A.J.; Kolesar, J.M. Lapatinib: a small-molecule inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor-2 tyrosine kinases used in the treatment of breast cancer. Clin. Ther., 2009, 31(Pt 2), 2332-2348.
[http://dx.doi.org/10.1016/j.clinthera.2009.11.029] [PMID: 20110044]

Geyer, C.E.; Forster, J.; Lindquist, D.; Chan, S.; Romieu, C.G.; Pienkowski, T.; Jagiello-Gruszfeld, A.; Crown, J.; Chan, A.; Kaufman, B.; Skarlos, D.; Campone, M.; Davidson, N.; Berger, M.; Oliva, C.; Rubin, S.D.; Stein, S.; Cameron, D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N. Engl. J. Med., 2006, 355(26), 2733-2743.
[http://dx.doi.org/10.1056/NEJMoa064320] [PMID: 17192538]

Voigtlaender, M.; Schneider-Merck, T.; Trepel, M. Lapatinib. Recent Results Cancer Res., 2018, 211, 19-44.
[http://dx.doi.org/10.1007/978-3-319-91442-8_2] [PMID: 30069757]

Taskar, K.S.; Rudraraju, V.; Mittapalli, R.K.; Samala, R.; Thorsheim, H.R.; Lockman, J.; Gril, B.; Hua, E.; Palmieri, D.; Polli, J.W.; Castellino, S.; Rubin, S.D.; Lockman, P.R.; Steeg, P.S.; Smith, Q.R. Lapatinib distribution in HER2 overexpressing experimental brain metastases of breast cancer. Pharm. Res., 2012, 29(3), 770-781.
[http://dx.doi.org/10.1007/s11095-011-0601-8] [PMID: 22011930]

Bian, L.; Wang, T.; Zhang, S.; Jiang, Z. Trastuzumab plus capecitabine vs. lapatinib plus capecitabine in patients with trastuzumab resistance and taxane-pretreated metastatic breast cancer. Tumour Biol., 2013, 34(5), 3153-3158.
[http://dx.doi.org/10.1007/s13277-013-0884-y] [PMID: 23729232]

D’Amato, V.; Raimondo, L.; Formisano, L.; Giuliano, M.; De Placido, S.; Rosa, R.; Bianco, R. Mechanisms of lapatinib resistance in HER2-driven breast cancer. Cancer Treat. Rev., 2015, 41(10), 877-883.
[http://dx.doi.org/10.1016/j.ctrv.2015.08.001] [PMID: 26276735]

Sergina, N.V.; Rausch, M.; Wang, D.; Blair, J.; Hann, B.; Shokat, K.M.; Moasser, M.M. Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3. Nature, 2007, 445(7126), 437-441.
[http://dx.doi.org/10.1038/nature05474] [PMID: 17206155]

Hegde, P.S.; Rusnak, D.; Bertiaux, M.; Alligood, K.; Strum, J.; Gagnon, R.; Gilmer, T.M. Delineation of molecular mechanisms of sensitivity to lapatinib in breast cancer cell lines using global gene expression profiles. Mol. Cancer Ther., 2007, 6(5), 1629-1640.
[http://dx.doi.org/10.1158/1535-7163.MCT-05-0399] [PMID: 17513611]

Elster, N.; Cremona, M.; Morgan, C.; Toomey, S.; Carr, A.; O’Grady, A.; Hennessy, B.T.; Eustace, A.J. A preclinical evaluation of the PI3K alpha/delta dominant inhibitor BAY 80-6946 in HER2-positive breast cancer models with acquired resistance to the HER2-targeted therapies trastuzumab and lapatinib. Breast Cancer Res. Treat., 2015, 149(2), 373-383.
[http://dx.doi.org/10.1007/s10549-014-3239-5] [PMID: 25528022]

Rexer, B.N.; Ham, A.J.; Rinehart, C.; Hill, S.; Granja-Ingram, N.M.; González-Angulo, A.M.; Mills, G.B.; Dave, B.; Chang, J.C.; Liebler, D.C.; Arteaga, C.L. Phosphoproteomic mass spectrometry profiling links Src family kinases to escape from HER2 tyrosine kinase inhibition. Oncogene, 2011, 30(40), 4163-4174.
[http://dx.doi.org/10.1038/onc.2011.130] [PMID: 21499296]

Roskoski, R., Jr Src protein-tyrosine kinase structure, mechanism, and small molecule inhibitors. Pharmacol. Res., 2015, 94, 9-25.
[http://dx.doi.org/10.1016/j.phrs.2015.01.003] [PMID: 25662515]

Elsberger, B. Translational evidence on the role of Src kinase and activated Src kinase in invasive breast cancer. Crit. Rev. Oncol. Hematol., 2014, 89(3), 343-351.
[http://dx.doi.org/10.1016/j.critrevonc.2013.12.009] [PMID: 24388104]

Liu, L.; Greger, J.; Shi, H.; Liu, Y.; Greshock, J.; Annan, R.; Halsey, W.; Sathe, G.M.; Martin, A.M.; Gilmer, T.M. Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL. Cancer Res., 2009, 69(17), 6871-6878.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-4490] [PMID: 19671800]

Chen, C.T.; Kim, H.; Liska, D.; Gao, S.; Christensen, J.G.; Weiser, M.R. MET activation mediates resistance to lapatinib inhibition of HER2-amplified gastric cancer cells. Mol. Cancer Ther., 2012, 11(3), 660-669.
[http://dx.doi.org/10.1158/1535-7163.MCT-11-0754] [PMID: 22238368]

Brady, S.W.; Zhang, J.; Tsai, M.H.; Yu, D. PI3K-independent mTOR activation promotes lapatinib resistance and IAP expression that can be effectively reversed by mTOR and Hsp90 inhibition. Cancer Biol. Ther., 2015, 16(3), 402-411.
[http://dx.doi.org/10.1080/15384047.2014.1002693] [PMID: 25692408]

Trowe, T.; Boukouvala, S.; Calkins, K.; Cutler, R.E., Jr; Fong, R.; Funke, R.; Gendreau, S.B.; Kim, Y.D.; Miller, N.; Woolfrey, J.R.; Vysotskaia, V.; Yang, J.P.; Gerritsen, M.E.; Matthews, D.J.; Lamb, P.; Heuer, T.S. EXEL-7647 inhibits mutant forms of ErbB2 associated with lapatinib resistance and neoplastic transformation. Clin. Cancer Res., 2008, 14(8), 2465-2475.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-4367] [PMID: 18413839]

Wetterskog, D.; Shiu, K.K.; Chong, I.; Meijer, T.; Mackay, A.; Lambros, M.; Cunningham, D.; Reis-Filho, J.S.; Lord, C.J.; Ashworth, A. Identification of novel determinants of resistance to lapatinib in ERBB2-amplified cancers. Oncogene, 2014, 33(8), 966-976.
[http://dx.doi.org/10.1038/onc.2013.41] [PMID: 23474757]

Nishimura, R.; Arima, N. Is triple negative a prognostic factor in breast cancer? Breast Cancer, 2008, 15(4), 303-308.
[http://dx.doi.org/10.1007/s12282-008-0042-3] [PMID: 18369692]

Denkert, C.; Liedtke, C.; Tutt, A.; von Minckwitz, G. Molecular alterations in triple-negative breast cancer-the road to new treatment strategies. Lancet, 2017, 389(10087), 2430-2442.
[http://dx.doi.org/10.1016/S0140-6736(16)32454-0] [PMID: 27939063]

Sørlie, T.; Perou, C.M.; Tibshirani, R.; Aas, T.; Geisler, S.; Johnsen, H.; Hastie, T.; Eisen, M.B.; van de Rijn, M.; Jeffrey, S.S.; Thorsen, T.; Quist, H.; Matese, J.C.; Brown, P.O.; Botstein, D.; Lønning, P.E.; Børresen-Dale, A.L. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc. Natl. Acad. Sci. USA, 2001, 98(19), 10869-10874.
[http://dx.doi.org/10.1073/pnas.191367098] [PMID: 11553815]

Pareja, F.; Geyer, F.C.; Marchiò, C.; Burke, K.A.; Weigelt, B.; Reis-Filho, J.S. Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants. NPJ Breast Cancer, 2016, 2, 16036.
[http://dx.doi.org/10.1038/npjbcancer.2016.36] [PMID: 28721389]

Wein, L.; Loi, S. Mechanisms of resistance of chemotherapy in early-stage Triple Negative Breast Cancer (TNBC). Breast, 2017, 34(Suppl. 1), S27-S30.
[http://dx.doi.org/10.1016/j.breast.2017.06.023] [PMID: 28668293]

Isakoff, S.J. Triple-negative breast cancer: role of specific chemotherapy agents. Cancer J., 2010, 16(1), 53-61.
[http://dx.doi.org/10.1097/PPO.0b013e3181d24ff7] [PMID: 20164691]

Rivera, E. Implications of anthracycline-resistant and taxane-resistant metastatic breast cancer and new therapeutic options. Breast J., 2010, 16(3), 252-263.
[http://dx.doi.org/10.1111/j.1524-4741.2009.00896.x] [PMID: 20408828]

Zeichner, S.B.; Terawaki, H.; Gogineni, K. A review of systemic treatment in metastatic triple-negative breast cancer. Breast Cancer (Auckl.), 2016, 10, 25-36.
[http://dx.doi.org/10.4137/BCBCR.S32783] [PMID: 27042088]

Perez-Garcia, J.M.; Cortes, J. The safety of eribulin for the treatment of metastatic breast cancer. Expert Opin. Drug Saf., 2019, 18(5), 347-355.
[http://dx.doi.org/10.1080/14740338.2019.1608946] [PMID: 31107111]

Gregory, R.K.; Smith, I.E. Vinorelbine-a clinical review. Br. J. Cancer, 2000, 82(12), 1907-1913.
[PMID: 10864196]

Blum, J.L.; Jones, S.E.; Buzdar, A.U.; LoRusso, P.M.; Kuter, I.; Vogel, C.; Osterwalder, B.; Burger, H.U.; Brown, C.S.; Griffin, T. Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer. J. Clin. Oncol., 1999, 17(2), 485-493.
[http://dx.doi.org/10.1200/JCO.1999.17.2.485] [PMID: 10080589]

McGrogan, B.T.; Gilmartin, B.; Carney, D.N.; McCann, A. Taxanes, microtubules and chemoresistant breast cancer. Biochim. Biophys. Acta, 2008, 1785(2), 96-132.
[PMID: 18068131]

Assal, A.; Kaner, J.; Pendurti, G.; Zang, X. Emerging targets in cancer immunotherapy: beyond CTLA-4 and PD-1. Immunotherapy, 2015, 7(11), 1169-1186.
[http://dx.doi.org/10.2217/imt.15.78] [PMID: 26567614]

Schmid, P.; Adams, S.; Rugo, H.S.; Schneeweiss, A.; Barrios, C.H.; Iwata, H.; Diéras, V.; Hegg, R. Im, S.A.; Shaw Wright, G.; Henschel, V.; Molinero, L.; Chui, S.Y.; Funke, R.; Husain, A.; Winer, E.P.; Loi, S.; Emens, L.A. Atezolizumab and Nab-paclitaxel in advanced triple-negative breast cancer. N. Engl. J. Med., 2018, 379(22), 2108-2121.
[http://dx.doi.org/10.1056/NEJMoa1809615] [PMID: 30345906]

Heimes, A.S.; Schmidt, M. Atezolizumab for the treatment of triple-negative breast cancer. Expert Opin. Investig. Drugs, 2019, 28(1), 1-5.
[http://dx.doi.org/10.1080/13543784.2019.1552255] [PMID: 30474425]

Garg, A.D.; More, S.; Rufo, N.; Mece, O.; Sassano, M.L.; Agostinis, P.; Zitvogel, L.; Kroemer, G.; Galluzzi, L. Trial watch: immunogenic cell death induction by anticancer chemotherapeutics. OncoImmunology, 2017, 6(12),e1386829.
[http://dx.doi.org/10.1080/2162402X.2017.1386829] [PMID: 29209573]

Heinhuis, K.M.; Ros, W.; Kok, M.; Steeghs, N.; Beijnen, J.H.; Schellens, J.H.M. Enhancing antitumor response by combining immune checkpoint inhibitors with chemotherapy in solid tumors. Ann. Oncol., 2019, 30(2), 219-235.
[http://dx.doi.org/10.1093/annonc/mdy551] [PMID: 30608567]

Emens, L.A.; Middleton, G. The interplay of immunotherapy and chemotherapy: harnessing potential synergies. Cancer Immunol. Res., 2015, 3(5), 436-443.
[http://dx.doi.org/10.1158/2326-6066.CIR-15-0064] [PMID: 25941355]

Goodman, A.M.; Kato, S.; Bazhenova, L.; Patel, S.P.; Frampton, G.M.; Miller, V.; Stephens, P.J.; Daniels, G.A.; Kurzrock, R. Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol. Cancer Ther., 2017, 16(11), 2598-2608.
[http://dx.doi.org/10.1158/1535-7163.MCT-17-0386] [PMID: 28835386]

Barroso-Sousa, R.; Jain, E.; Cohen, O.; Kim, D.; Buendia-Buendia, J.; Winer, E.; Lin, N.; Tolaney, S.M.; Wagle, N. Prevalence and mutational determinants of high tumor mutation burden in breast cancer. Ann. Oncol., 2020, 31(3), 387-394.
[http://dx.doi.org/10.1016/j.annonc.2019.11.010] [PMID: 32067680]

García-Teijido, P.; Cabal, M.L.; Fernández, I.P.; Pérez, Y.F. Tumor-infiltrating Lymphocytes in triple negative breast cancer: the future of immune targeting. Clin. Med. Insights Oncol., 2016, 10(Suppl. 1), 31-39.
[http://dx.doi.org/10.4137/CMO.S34540] [PMID: 27081325]

Dushyanthen, S.; Beavis, P.A.; Savas, P.; Teo, Z.L.; Zhou, C.; Mansour, M.; Darcy, P.K.; Loi, S. Relevance of tumor-infiltrating lymphocytes in breast cancer. BMC Med., 2015, 13, 202.
[http://dx.doi.org/10.1186/s12916-015-0431-3] [PMID: 26300242]

Lee, H.J.; Park, I.A.; Song, I.H.; Shin, S.J.; Kim, J.Y.; Yu, J.H.; Gong, G. Tertiary lymphoid structures: prognostic significance and relationship with tumour-infiltrating lymphocytes in triple-negative breast cancer. J. Clin. Pathol., 2016, 69(5), 422-430.
[http://dx.doi.org/10.1136/jclinpath-2015-203089] [PMID: 26475777]

Seo, A.N.; Lee, H.J.; Kim, E.J.; Kim, H.J.; Jang, M.H.; Lee, H.E.; Kim, Y.J.; Kim, J.H.; Park, S.Y. Tumour-infiltrating CD8+ lymphocytes as an independent predictive factor for pathological complete response to primary systemic therapy in breast cancer. Br. J. Cancer, 2013, 109(10), 2705-2713.
[http://dx.doi.org/10.1038/bjc.2013.634] [PMID: 24129232]

Loi, S.; Dushyanthen, S.; Beavis, P.A.; Salgado, R.; Denkert, C.; Savas, P.; Combs, S.; Rimm, D.L.; Giltnane, J.M.; Estrada, M.V.; Sánchez, V.; Sanders, M.E.; Cook, R.S.; Pilkinton, M.A.; Mallal, S.A.; Wang, K.; Miller, V.A.; Stephens, P.J.; Yelensky, R.; Doimi, F.D.; Gómez, H.; Ryzhov, S.V.; Darcy, P.K.; Arteaga, C.L.; Balko, J.M. RAS/MAPK activation is associated with reduced tumor-infiltrating lymphocytes in triple-negative breast cancer: therapeutic cooperation between MEK and PD-1/PD-L1 immune checkpoint inhibitors. Clin. Cancer Res., 2016, 22(6), 1499-1509.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-1125] [PMID: 26515496]

Tomioka, N.; Azuma, M.; Ikarashi, M.; Yamamoto, M.; Sato, M.; Watanabe, K.I.; Yamashiro, K.; Takahashi, M. The therapeutic candidate for immune checkpoint inhibitors elucidated by the status of Tumor-Infiltrating Lymphocytes (TILs) and Programmed Death Ligand 1 (PD-L1) expression in Triple Negative Breast Cancer (TNBC). Breast Cancer, 2018, 25(1), 34-42.
[http://dx.doi.org/10.1007/s12282-017-0781-0] [PMID: 28488168]

Kim, I.S.; Gao, Y.; Welte, T.; Wang, H.; Liu, J.; Janghorban, M.; Sheng, K.; Niu, Y.; Goldstein, A.; Zhao, N.; Bado, I.; Lo, H.C.; Toneff, M.J.; Nguyen, T.; Bu, W.; Jiang, W.; Arnold, J.; Gu, F.; He, J.; Jebakumar, D.; Walker, K.; Li, Y.; Mo, Q.; Westbrook, T.F.; Zong, C.; Rao, A.; Sreekumar, A.; Rosen, J.M.; Zhang, X.H. Immuno-subtyping of breast cancer reveals distinct myeloid cell profiles and immunotherapy resistance mechanisms. Nat. Cell Biol., 2019, 21(9), 1113-1126.
[http://dx.doi.org/10.1038/s41556-019-0373-7] [PMID: 31451770]

Peng, W.; Chen, J.Q.; Liu, C.; Malu, S.; Creasy, C.; Tetzlaff, M.T.; Xu, C.; McKenzie, J.A.; Zhang, C.; Liang, X.; Williams, L.J.; Deng, W.; Chen, G.; Mbofung, R.; Lazar, A.J.; Torres-Cabala, C.A.; Cooper, Z.A.; Chen, P.L.; Tieu, T.N.; Spranger, S.; Yu, X.; Bernatchez, C.; Forget, M.A.; Haymaker, C.; Amaria, R.; McQuade, J.L.; Glitza, I.C.; Cascone, T.; Li, H.S.; Kwong, L.N.; Heffernan, T.P.; Hu, J.; Bassett, R.L., Jr; Bosenberg, M.W.; Woodman, S.E.; Overwijk, W.W.; Lizée, G.; Roszik, J.; Gajewski, T.F.; Wargo, J.A.; Gershenwald, J.E.; Radvanyi, L.; Davies, M.A.; Hwu, P. Loss of PTEN promotes resistance to T cell-mediated immunotherapy. Cancer Discov., 2016, 6(2), 202-216.
[http://dx.doi.org/10.1158/2159-8290.CD-15-0283] [PMID: 26645196]

Barroso-Sousa, R.; Keenan, T.E.; Pernas, S.; Exman, P.; Jain, E.; Garrido-Castro, A.C.; Hughes, M.; Bychkovsky, B.; Umeton, R.; Files, J.L.; Lindeman, N.I.; MacConaill, L.E.; Hodi, F.S.; Krop, I.E.; Dillon, D.; Winer, E.P.; Wagle, N.; Lin, N.U.; Mittendorf, E.A.; Van Allen, E.M.; Tolaney, S.M. Tumor mutational burden and PTEN alterations as molecular correlates of response to PD-1/L1 blockade in metastatic triple-negative breast cancer. Clin. Cancer Res., 2020, 26(11), 2565-2572.
[http://dx.doi.org/10.1158/1078-0432.CCR-19-3507] [PMID: 32019858]

Gudmundsdottir, K.; Ashworth, A. The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability. Oncogene, 2006, 25(43), 5864-5874.
[http://dx.doi.org/10.1038/sj.onc.1209874] [PMID: 16998501]

Gonzalez-Angulo, A.M.; Timms, K.M.; Liu, S.; Chen, H.; Litton, J.K.; Potter, J.; Lanchbury, J.S.; Stemke-Hale, K.; Hennessy, B.T.; Arun, B.K.; Hortobagyi, G.N.; Do, K.A.; Mills, G.B.; Meric-Bernstam, F. Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer. Clin. Cancer Res., 2011, 17(5), 1082-1089.
[http://dx.doi.org/10.1158/1078-0432.CCR-10-2560] [PMID: 21233401]

Robson, M.; Im, S.A.; Senkus, E.; Xu, B.; Domchek, S.M.; Masuda, N.; Delaloge, S.; Li, W.; Tung, N.; Armstrong, A.; Wu, W.; Goessl, C.; Runswick, S.; Conte, P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N. Engl. J. Med., 2017, 377(6), 523-533.
[http://dx.doi.org/10.1056/NEJMoa1706450] [PMID: 28578601]

Litton, J.K.; Rugo, H.S.; Ettl, J.; Hurvitz, S.A.; Gonçalves, A.; Lee, K.H.; Fehrenbacher, L.; Yerushalmi, R.; Mina, L.A.; Martin, M.; Roché, H.; Im, Y.H.; Quek, R.G.W.; Markova, D.; Tudor, I.C.; Hannah, A.L.; Eiermann, W.; Blum, J.L. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N. Engl. J. Med., 2018, 379(8), 753-763.
[http://dx.doi.org/10.1056/NEJMoa1802905] [PMID: 30110579]

Noordermeer, S.M.; van Attikum, H. PARP inhibitor resistance: a tug-of-war in BRCA-mutated cells. Trends Cell Biol., 2019, 29(10), 820-834.
[http://dx.doi.org/10.1016/j.tcb.2019.07.008] [PMID: 31421928]

Christie, E.L.; Pattnaik, S.; Beach, J.; Copeland, A.; Rashoo, N.; Fereday, S.; Hendley, J.; Alsop, K.; Brady, S.L.; Lamb, G.; Pandey, A.; deFazio, A.; Thorne, H.; Bild, A.; Bowtell, D.D.L. Multiple ABCB1 transcriptional fusions in drug resistant high-grade serous ovarian and breast cancer. Nat. Commun., 2019, 10(1), 1295.
[http://dx.doi.org/10.1038/s41467-019-09312-9] [PMID: 30894541]

Rottenberg, S.; Jaspers, J.E.; Kersbergen, A.; van der Burg, E.; Nygren, A.O.; Zander, S.A.; Derksen, P.W.; de Bruin, M.; Zevenhoven, J.; Lau, A.; Boulter, R.; Cranston, A.; O’Connor, M.J.; Martin, N.M.; Borst, P.; Jonkers, J. High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs. Proc. Natl. Acad. Sci. USA, 2008, 105(44), 17079-17084.
[http://dx.doi.org/10.1073/pnas.0806092105] [PMID: 18971340]

Oplustilova, L.; Wolanin, K.; Mistrik, M.; Korinkova, G.; Simkova, D.; Bouchal, J.; Lenobel, R.; Bartkova, J.; Lau, A.; O’Connor, M.J.; Lukas, J.; Bartek, J. Evaluation of candidate biomarkers to predict cancer cell sensitivity or resistance to PARP-1 inhibitor treatment. Cell Cycle, 2012, 11(20), 3837-3850.
[http://dx.doi.org/10.4161/cc.22026] [PMID: 22983061]

Du, Y.; Yamaguchi, H.; Wei, Y.; Hsu, J.L.; Wang, H.L.; Hsu, Y.H.; Lin, W.C.; Yu, W.H.; Leonard, P.G.; Lee, G.R., IV; Chen, M.K.; Nakai, K.; Hsu, M.C.; Chen, C.T.; Sun, Y.; Wu, Y.; Chang, W.C.; Huang, W.C.; Liu, C.L.; Chang, Y.C.; Chen, C.H.; Park, M.; Jones, P.; Hortobagyi, G.N.; Hung, M.C. Blocking c-Met-mediated PARP1 phosphorylation enhances anti-tumor effects of PARP inhibitors. Nat. Med., 2016, 22(2), 194-201.
[http://dx.doi.org/10.1038/nm.4032] [PMID: 26779812]

Gogola, E.; Duarte, A.A.; de Ruiter, J.R.; Wiegant, W.W.; Schmid, J.A.; de Bruijn, R.; James, D.I.; Guerrero Llobet, S.; Vis, D.J.; Annunziato, S.; van den Broek, B.; Barazas, M.; Kersbergen, A.; van de Ven, M.; Tarsounas, M.; Ogilvie, D.J.; van Vugt, M.; Wessels, L.F.A.; Bartkova, J.; Gromova, I.; Andújar-Sánchez, M.; Bartek, J.; Lopes, M.; van Attikum, H.; Borst, P.; Jonkers, J.; Rottenberg, S. Selective loss of PARG restores PARylation and counteracts PARP inhibitor-mediated synthetic lethality. Cancer Cell, 2018, 33(6), 1078-1093.
[http://dx.doi.org/10.1016/j.ccell.2018.05.008] [PMID: 29894693]

Pettitt, S.J.; Krastev, D.B.; Brandsma, I.; Dréan, A.; Song, F.; Aleksandrov, R.; Harrell, M.I.; Menon, M.; Brough, R.; Campbell, J.; Frankum, J.; Ranes, M.; Pemberton, H.N.; Rafiq, R.; Fenwick, K.; Swain, A.; Guettler, S.; Lee, J.M.; Swisher, E.M.; Stoynov, S.; Yusa, K.; Ashworth, A.; Lord, C.J. Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance. Nat. Commun., 2018, 9(1), 1849.
[http://dx.doi.org/10.1038/s41467-018-03917-2] [PMID: 29748565]

Norquist, B.; Wurz, K.A.; Pennil, C.C.; Garcia, R.; Gross, J.; Sakai, W.; Karlan, B.Y.; Taniguchi, T.; Swisher, E.M. Secondary somatic mutations restoring BRCA1/2 predict chemotherapy resistance in hereditary ovarian carcinomas. J. Clin. Oncol., 2011, 29(22), 3008-3015.
[http://dx.doi.org/10.1200/JCO.2010.34.2980] [PMID: 21709188]

Lin, K.K.; Harrell, M.I.; Oza, A.M.; Oaknin, A.; Ray-Coquard, I.; Tinker, A.V.; Helman, E.; Radke, M.R.; Say, C.; Vo, L.T.; Mann, E.; Isaacson, J.D.; Maloney, L.; O’Malley, D.M.; Chambers, S.K.; Kaufmann, S.H.; Scott, C.L.; Konecny, G.E.; Coleman, R.L.; Sun, J.X.; Giordano, H.; Brenton, J.D.; Harding, T.C.; McNeish, I.A.; Swisher, E.M. BRCA reversion mutations in circulating tumor DNA predict primary and acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma. Cancer Discov., 2019, 9(2), 210-219.
[http://dx.doi.org/10.1158/2159-8290.CD-18-0715] [PMID: 30425037]

Gornstein, E.L.; Sandefur, S.; Chung, J.H.; Gay, L.M.; Holmes, O.; Erlich, R.L.; Soman, S.; Martin, L.K.; Rose, A.V.; Stephens, P.J.; Ross, J.S.; Miller, V.A.; Ali, S.M.; Blau, S. BRCA2 reversion mutation associated with acquired resistance to olaparib in estrogen receptor-positive breast cancer detected by genomic profiling of tissue and liquid biopsy. Clin. Breast Cancer, 2018, 18(2), 184-188.
[http://dx.doi.org/10.1016/j.clbc.2017.12.010] [PMID: 29325860]

Quigley, D.; Alumkal, J.J.; Wyatt, A.W.; Kothari, V.; Foye, A.; Lloyd, P.; Aggarwal, R.; Kim, W.; Lu, E.; Schwartzman, J.; Beja, K.; Annala, M.; Das, R.; Diolaiti, M.; Pritchard, C.; Thomas, G.; Tomlins, S.; Knudsen, K.; Lord, C.J.; Ryan, C.; Youngren, J.; Beer, T.M.; Ashworth, A.; Small, E.J.; Feng, F.Y. Analysis of circulating cell-free DNA identifies multiclonal heterogeneity of BRCA2 reversion mutations associated with resistance to PARP inhibitors. Cancer Discov., 2017, 7(9), 999-1005.
[http://dx.doi.org/10.1158/2159-8290.CD-17-0146] [PMID: 28450426]

Edwards, S.L.; Brough, R.; Lord, C.J.; Natrajan, R.; Vatcheva, R.; Levine, D.A.; Boyd, J.; Reis-Filho, J.S.; Ashworth, A. Resistance to therapy caused by intragenic deletion in BRCA2. Nature, 2008, 451(7182), 1111-1115.
[http://dx.doi.org/10.1038/nature06548] [PMID: 18264088]

Lheureux, S.; Bruce, J.P.; Burnier, J.V.; Karakasis, K.; Shaw, P.A.; Clarke, B.A.; Yang, S.Y.; Quevedo, R.; Li, T.; Dowar, M.; Bowering, V.; Pugh, T.J.; Oza, A.M. Somatic BRCA1/2 recovery as a resistance mechanism after exceptional response to poly (ADP-ribose) polymerase inhibition. J. Clin. Oncol., 2017, 35(11), 1240-1249.
[http://dx.doi.org/10.1200/JCO.2016.71.3677] [PMID: 28221868]

Ter Brugge, P.; Kristel, P.; van der Burg, E.; Boon, U.; de Maaker, M.; Lips, E.; Mulder, L.; de Ruiter, J.; Moutinho, C.; Gevensleben, H.; Marangoni, E.; Majewski, I.; Józwiak, K.; Kloosterman, W.; van Roosmalen, M.; Duran, K.; Hogervorst, F.; Turner, N.; Esteller, M.; Cuppen, E.; Wesseling, J.; Jonkers, J. Mechanisms of therapy resistance in patient-derived xenograft models of BRCA1-deficient breast cancer. J. Natl. Cancer Inst., 2016, 108(11),djw148.
[http://dx.doi.org/10.1093/jnci/djw148] [PMID: 27381626]

Weigelt, B.; Comino-Méndez, I.; de Bruijn, I.; Tian, L.; Meisel, J.L.; García-Murillas, I.; Fribbens, C.; Cutts, R.; Martelotto, L.G.; Ng, C.K.Y.; Lim, R.S.; Selenica, P.; Piscuoglio, S.; Aghajanian, C.; Norton, L.; Murali, R.; Hyman, D.M.; Borsu, L.; Arcila, M.E.; Konner, J.; Reis-Filho, J.S.; Greenberg, R.A.; Robson, M.E.; Turner, N.C. Diverse BRCA1 and BRCA2 reversion mutations in circulating cell-free DNA of therapy-resistant breast or ovarian cancer. Clin. Cancer Res., 2017, 23(21), 6708-6720.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0544] [PMID: 28765325]

Simmons, A.D.; Nguyen, M.; Pintus, E. Polyclonal BRCA2 mutations following carboplatin treatment confer resistance to the PARP inhibitor rucaparib in a patient with mCRPC: a case report. BMC Cancer, 2020, 20(1), 215.
[http://dx.doi.org/10.1186/s12885-020-6657-2] [PMID: 32171277]

Mayor, P.; Gay, L.M.; Lele, S.; Elvin, J.A. BRCA1 reversion mutation acquired after treatment identified by liquid biopsy. Gynecol. Oncol. Rep., 2017, 21, 57-60.
[http://dx.doi.org/10.1016/j.gore.2017.06.010] [PMID: 28706968]

Goodall, J.; Mateo, J.; Yuan, W.; Mossop, H.; Porta, N.; Miranda, S.; Perez-Lopez, R.; Dolling, D.; Robinson, D.R.; Sandhu, S.; Fowler, G.; Ebbs, B.; Flohr, P.; Seed, G.; Rodrigues, D.N.; Boysen, G.; Bertan, C.; Atkin, M.; Clarke, M.; Crespo, M.; Figueiredo, I.; Riisnaes, R.; Sumanasuriya, S.; Rescigno, P.; Zafeiriou, Z.; Sharp, A.; Tunariu, N.; Bianchini, D.; Gillman, A.; Lord, C.J.; Hall, E.; Chinnaiyan, A.M.; Carreira, S.; de Bono, J.S. Circulating cell-free DNA to guide prostate cancer treatment with PARP inhibition. Cancer Discov., 2017, 7(9), 1006-1017.
[http://dx.doi.org/10.1158/2159-8290.CD-17-0261] [PMID: 28450425]

Berti, M.; Ray Chaudhuri, A.; Thangavel, S.; Gomathinayagam, S.; Kenig, S.; Vujanovic, M.; Odreman, F.; Glatter, T.; Graziano, S.; Mendoza-Maldonado, R.; Marino, F.; Lucic, B.; Biasin, V.; Gstaiger, M.; Aebersold, R.; Sidorova, J.M.; Monnat, R.J., Jr; Lopes, M.; Vindigni, A. Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition. Nat. Struct. Mol. Biol., 2013, 20(3), 347-354.
[http://dx.doi.org/10.1038/nsmb.2501] [PMID: 23396353]

Schlacher, K.; Christ, N.; Siaud, N.; Egashira, A.; Wu, H.; Jasin, M. Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11. Cell, 2011, 145(4), 529-542.
[http://dx.doi.org/10.1016/j.cell.2011.03.041] [PMID: 21565612]

Schlacher, K.; Wu, H.; Jasin, M. A distinct replication fork protection pathway connects Fanconi anemia tumor suppressors to RAD51-BRCA1/2. Cancer Cell, 2012, 22(1), 106-116.
[http://dx.doi.org/10.1016/j.ccr.2012.05.015] [PMID: 22789542]

Ying, S.; Hamdy, F.C.; Helleday, T. Mre11-dependent degradation of stalled DNA replication forks is prevented by BRCA2 and PARP1. Cancer Res., 2012, 72(11), 2814-2821.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-3417] [PMID: 22447567]

Rondinelli, B.; Gogola, E.; Yücel, H.; Duarte, A.A.; van de Ven, M.; van der Sluijs, R.; Konstantinopoulos, P.A.; Jonkers, J.; Ceccaldi, R.; Rottenberg, S.; D’Andrea, A.D. EZH2 promotes degradation of stalled replication forks by recruiting MUS81 through histone H3 trimethylation. Nat. Cell Biol., 2017, 19(11), 1371-1378.
[http://dx.doi.org/10.1038/ncb3626] [PMID: 29035360]

Block, K.I.; Gyllenhaal, C.; Lowe, L.; Amedei, A.; Amin, A.R.M.R.; Amin, A.; Aquilano, K.; Arbiser, J.; Arreola, A.; Arzumanyan, A.; Ashraf, S.S.; Azmi, A.S.; Benencia, F.; Bhakta, D.; Bilsland, A.; Bishayee, A.; Blain, S.W.; Block, P.B.; Boosani, C.S.; Carey, T.E.; Carnero, A.; Carotenuto, M.; Casey, S.C.; Chakrabarti, M.; Chaturvedi, R.; Chen, G.Z.; Chen, H.; Chen, S.; Chen, Y.C.; Choi, B.K.; Ciriolo, M.R.; Coley, H.M.; Collins, A.R.; Connell, M.; Crawford, S.; Curran, C.S.; Dabrosin, C.; Damia, G.; Dasgupta, S.; DeBerardinis, R.J.; Decker, W.K.; Dhawan, P.; Diehl, A.M.E.; Dong, J.T.; Dou, Q.P.; Drew, J.E.; Elkord, E.; El-Rayes, B.; Feitelson, M.A.; Felsher, D.W.; Ferguson, L.R.; Fimognari, C.; Firestone, G.L.; Frezza, C.; Fujii, H.; Fuster, M.M.; Generali, D.; Georgakilas, A.G.; Gieseler, F.; Gilbertson, M.; Green, M.F.; Grue, B.; Guha, G.; Halicka, D.; Helferich, W.G.; Heneberg, P.; Hentosh, P.; Hirschey, M.D.; Hofseth, L.J.; Holcombe, R.F.; Honoki, K.; Hsu, H.Y.; Huang, G.S.; Jensen, L.D.; Jiang, W.G.; Jones, L.W.; Karpowicz, P.A.; Keith, W.N.; Kerkar, S.P.; Khan, G.N.; Khatami, M.; Ko, Y.H.; Kucuk, O.; Kulathinal, R.J.; Kumar, N.B.; Kwon, B.S.; Le, A.; Lea, M.A.; Lee, H.Y.; Lichtor, T.; Lin, L.T.; Locasale, J.W.; Lokeshwar, B.L.; Longo, V.D.; Lyssiotis, C.A.; MacKenzie, K.L.; Malhotra, M.; Marino, M.; Martinez-Chantar, M.L.; Matheu, A.; Maxwell, C.; McDonnell, E.; Meeker, A.K.; Mehrmohamadi, M.; Mehta, K.; Michelotti, G.A.; Mohammad, R.M.; Mohammed, S.I.; Morre, D.J.; Muralidhar, V.; Muqbil, I.; Murphy, M.P.; Nagaraju, G.P.; Nahta, R.; Niccolai, E.; Nowsheen, S.; Panis, C.; Pantano, F.; Parslow, V.R.; Pawelec, G.; Pedersen, P.L.; Poore, B.; Poudyal, D.; Prakash, S.; Prince, M.; Raffaghello, L.; Rathmell, J.C.; Rathmell, W.K.; Ray, S.K.; Reichrath, J.; Rezazadeh, S.; Ribatti, D.; Ricciardiello, L.; Robey, R.B.; Rodier, F.; Rupasinghe, H.P.V.; Russo, G.L.; Ryan, E.P.; Samadi, A.K.; Sanchez-Garcia, I.; Sanders, A.J.; Santini, D.; Sarkar, M.; Sasada, T.; Saxena, N.K.; Shackelford, R.E.; Shantha Kumara, H.M.C.; Sharma, D.; Shin, D.M.; Sidransky, D.; Siegelin, M.D.; Signori, E.; Singh, N.; Sivanand, S.; Sliva, D.; Smythe, C.; Spagnuolo, C.; Stafforini, D.M.; Stagg, J.; Subbarayan, P.R.; Sundin, T.; Talib, W.H.; Thompson, S.K.; Tran, P.T.; Ungefroren, H.; Vander Heiden, M.G.; Venkateswaran, V.; Vinay, D.S.; Vlachostergios, P.J.; Wang, Z.; Wellen, K.E.; Whelan, R.L.; Yang, E.S.; Yang, H.; Yang, X.; Yaswen, P.; Yedjou, C.; Yin, X.; Zhu, J.; Zollo, M. Designing a broad-spectrum integrative approach for cancer prevention and treatment. Semin. Cancer Biol., 2015, 35(Suppl.), S276-S304.
[http://dx.doi.org/10.1016/j.semcancer.2015.09.007] [PMID: 26590477]