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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

The Pharmacogenomics “Side-effect” of TP53/EGFR in Non-small Cell Lung Cancer Accompanied with Atorvastatin Therapy: A Functional Network Analysis

Author(s): Lei Zhang, Yifang Huang, Xuedong Gan, Siying He, Xiaohuan Cheng, Na Yang, Siwei Li, Zuhua Li and Fang Zheng*

Volume 19, Issue 17, 2019

Page: [2060 - 2071] Pages: 12

DOI: 10.2174/1871520619666190712203217

Price: $65


Background: Atorvastatin belongs to the group of statins and is the leading drug for hypercholesterolemia treatment. Although, its anticancer effects are highly appreciated, its properties are still unclear. The aim of this study was to explore the underlying anticancer mechanisms induced by atorvastatin and enlarge the potential target in non-small cell lung cancer.

Methods: Target genes of atorvastatin were collected by the DrugBank database. Prediction of interaction between primary targets and secondary targets was performed, and protein-protein interaction network was constructed though the STRING. Then, KEGG pathway enrichment analysis was performed with WebGestalt and ClueGO, including the pathways in non-small cell lung cancer. Furthermore, a genomic alteration analysis of the selected seed genes of atorvastatin benefit and non-small cell lung cancer pathway was conducted by cBioPortal. Finally, a survival analysis with the selected seed genes in lung cancer (lung adenocarcinoma, lung squamous cell carcinoma) was conducted using Kaplan-Meier (KM) plotter.

Results: To identify seed genes, 65 potential candidate genes were screened as targets for atorvastatin using STRING with DrugBank database, while the KEGG pathway was enriched to get the overlap match of pathways in non-small cell lung cancer. Then 4 seed genes, Epidermal Growth Factor Receptor (EGFR), erb-b2 receptor tyrosine kinase 2 (ERBB2), AKT serine/threonine kinase 1 (AKT1) and tumor protein p53 (TP53), were selected and their genomic alternation were evaluated by cBioPortal. Survival analysis found that TP53 and EGFR showed a significant correlation (log rank P = 3e-07 and 0.023) with lung adenocarcinoma and lung squamous cell carcinoma, according to the KM analysis.

Conclusion: Gene-phenotype connectivity for atorvastatin in non-small cell lung cancer was identified using functional/activity network analysis method, and our findings demonstrated that TP53 and EGFR could be the potential targets in cancer patients with atorvastatin therapy.

Keywords: Atorvastatin, functional/activity network analysis, non-small cell lung cancer, TP53, EGFR, AKT1.

Graphical Abstract
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell, 2011, 144(5), 646-674.
[] [PMID: 21376230]
Mohan, A.; Harris, K.; Bowling, M.R.; Brown, C.; Hohenforst-Schmidt, W. Therapeutic bronchoscopy in the era of genotype directed lung cancer management. J. Thorac. Dis., 2018, 10(11), 6298-6309.
[] [PMID: 30622805]
Collins, R.; Reith, C.; Emberson, J.; Armitage, J.; Baigent, C.; Blackwell, L.; Blumenthal, R.; Danesh, J.; Smith, G.D.; DeMets, D.; Evans, S.; Law, M.; MacMahon, S.; Martin, S.; Neal, B.; Poulter, N.; Preiss, D.; Ridker, P.; Roberts, I.; Rodgers, A.; Sandercock, P.; Schulz, K.; Sever, P.; Simes, J.; Smeeth, L.; Wald, N.; Yusuf, S.; Peto, R. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet, 2016, 388(10059), 2532-2561.
[] [PMID: 27616593]
Eisenberg, D.A. Cholesterol lowering in the management of coronary artery disease: The clinical implications of recent trials. Am. J. Med., 1998, 104(2A)(Suppl. 1), 2S-5S.
[] [PMID: 9550499]
Graaf, M.R.; Beiderbeck, A.B.; Egberts, A.C.G.; Richel, D.J.; Guchelaar, H-J. The risk of cancer in users of statins. J. Clin. Oncol., 2004, 22(12), 2388-2394.
[] [PMID: 15197200]
Nielsen, S.F.; Nordestgaard, B.G.; Bojesen, S.E. Statin use and reduced cancer-related mortality. N. Engl. J. Med., 2012, 367(19), 1792-1802.
[] [PMID: 23134381]
Cardwell, C.R.; Mc Menamin, Ú.; Hughes, C.M.; Murray, L.J. Statin use and survival from lung cancer: A population-based cohort study. Cancer Epidemiol. Biomarkers Prev., 2015, 24(5), 833-841.
[] [PMID: 25934831]
Lin, J.J.; Ezer, N.; Sigel, K.; Mhango, G.; Wisnivesky, J.P. The effect of statins on survival in patients with stage IV lung cancer. Lung Cancer, 2016, 99, 137-142.
[] [PMID: 27565929]
Kwon, Y-J.; You, N-Y.; Lee, J-W.; Kim, J.; Kang, H-T. High receipt of statins reduces the risk of lung cancer in current smokers with hypercholesterolemia: The national health insurance service-health screening cohort. Clin. Lung Cancer, 2019, 20(2), e177-e185.
[] [PMID: 30578109]
Hsieh, T-C.; Wu, S-T.; Bennett, D.J.; Doonan, B.B.; Wu, E.; Wu, J.M. Functional/Activity Network (FAN) analysis of gene-phenotype connectivity liaised by grape polyphenol resveratrol. Oncotarget, 2016, 7(25), 38670-38680.
[] [PMID: 27232943]
Gyorffy, B.; Lanczky, A.; Eklund, A.C.; Denkert, C.; Budczies, J.; Li, Q.; Szallasi, Z. An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1809 patients. Breast Cancer Res. Treat., 2010, 123(3), 725-731.
Wishart, D.S.; Knox, C.; Guo, A.C.; Shrivastava, S.; Hassanali, M.; Stothard, P.; Chang, Z.; Woolsey, J. DrugBank: A comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res., 2006, 34(Database issue), D668-D672.
[] [PMID: 16381955]
Wishart, D.S.; Feunang, Y.D.; Guo, A.C.; Lo, E.J.; Marcu, A.; Grant, J.R.; Sajed, T.; Johnson, D.; Li, C.; Sayeeda, Z.; Assempour, N.; Iynkkaran, I.; Liu, Y.; Maciejewski, A.; Gale, N.; Wilson, A.; Chin, L.; Cummings, R.; Le, D.; Pon, A.; Knox, C.; Wilson, M. DrugBank 5.0: A major update to the DrugBank database for 2018. Nucleic Acids Res., 2018, 46(D1), D1074-D1082.
[] [PMID: 29126136]
Szklarczyk, D.; Morris, J.H.; Cook, H.; Kuhn, M.; Wyder, S.; Simonovic, M.; Santos, A.; Doncheva, N.T.; Roth, A.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res., 2017, 45(D1), D362-D368.
[] [PMID: 27924014]
Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res., 2003, 13(11), 2498-2504.
[] [PMID: 14597658]
Bing, Z.; Stefan, K.; Jay, S. An integrated system for exploring gene sets in various biological contexts. Nucleic Acids Res, 2005, 33(Web Server issue), W741-748.
Jing, W.; Dexter, D.; Zhiao, S.; Bing, Z. Web-based gene set analysis toolkit (webgestalt): Update 2013. Nucleic Acids Res, 2013, 41(Web Server issue), W714-718.
Gao, J.; Aksoy, B.A.; Dogrusoz, U.; Dresdner, G.; Gross, B.; Sumer, S.O.; Sun, Y.; Jacobsen, A.; Sinha, R.; Larsson, E.; Cerami, E.; Sander, C.; Schultz, N. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci. Signal., 2013, 6(269), pl1.
[] [PMID: 23550210]
Cerami, E.; Gao, J.; Dogrusoz, U.; Gross, B.E.; Sumer, S.O.; Aksoy, B.A.; Jacobsen, A.; Byrne, C.J.; Heuer, M.L.; Larsson, E.; Antipin, Y.; Reva, B.; Goldberg, A.P.; Sander, C.; Schultz, N. The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data. Cancer Discov., 2012, 2(5), 401-404.
[] [PMID: 22588877]
Lánczky, A.; Nagy, Á.; Bottai, G.; Munkácsy, G.; Szabó, A.; Santarpia, L.; Győrffy, B. miRpower: A web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients. Breast Cancer Res. Treat., 2016, 160(3), 439-446.
[] [PMID: 27744485]
Vavalà, T.; Monica, V.; Lo Iacono, M.; Mele, T.; Busso, S.; Righi, L.; Papotti, M.; Scagliotti, G.V.; Novello, S. Precision medicine in age-specific non-small-cell-lung-cancer patients: Integrating biomolecular results into clinical practice-A new approach to improve personalized translational research. Lung Cancer, 2017, 107, 84-90.
[] [PMID: 27346245]
Imielinski, M.; Berger, A.H.; Hammerman, P.S.; Hernandez, B.; Pugh, T.J.; Hodis, E.; Cho, J.; Suh, J.; Capelletti, M.; Sivachenko, A.; Sougnez, C.; Auclair, D.; Lawrence, M.S.; Stojanov, P.; Cibulskis, K.; Choi, K.; de Waal, L.; Sharifnia, T.; Brooks, A.; Greulich, H.; Banerji, S.; Zander, T.; Seidel, D.; Leenders, F.; Ansén, S.; Ludwig, C.; Engel-Riedel, W.; Stoelben, E.; Wolf, J.; Goparju, C.; Thompson, K.; Winckler, W.; Kwiatkowski, D.; Johnson, B.E.; Jänne, P.A.; Miller, V.A.; Pao, W.; Travis, W.D.; Pass, H.I.; Gabriel, S.B.; Lander, E.S.; Thomas, R.K.; Garraway, L.A.; Getz, G.; Meyerson, M. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell, 2012, 150(6), 1107-1120.
[] [PMID: 22980975]
Rizvi, N.A.; Hellmann, M.D.; Snyder, A.; Kvistborg, P.; Makarov, V.; Havel, J.J.; Lee, W.; Yuan, J.; Wong, P.; Ho, T.S.; Miller, M.L.; Rekhtman, N.; Moreira, A.L.; Ibrahim, F.; Bruggeman, C.; Gasmi, B.; Zappasodi, R.; Maeda, Y.; Sander, C.; Garon, E.B.; Merghoub, T.; Wolchok, J.D.; Schumacher, T.N.; Chan, T.A. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science, 2015, 348(6230), 124-128.
[] [PMID: 25765070]
The Cancer Genome Atlas Research, Collisson, E.A.; Campbell, J.D.; Brooks, A.N.; Berger, A.H.; Lee, W.; Chmielecki, J.; Beer, D.G.; Cope, L.; Creighton, C.J.; Danilova, L.; Ding, L.; Getz, G.; Hammerman, P.S, Hayes, D.N.; Hernandez, B.; Herman, J.G.; Heymach, J.V.; Jurisica, I.; Kucherlapati, R.; Kwiatkowski, D.; Ladanyi, M.; Robertson, G.; Schultz, N.; Shen, R.; Sinha, R.; Sougnez, C.; Tsao, M.S.; Travis, W.D.; Weinstein, J.N.; Wigle, D.A.; Wilkerson, M.D.; Chu, A.; Cherniack, A.D.; Hadjipanayis, A.; Rosenberg, M.; Weisenberger, D.J.; Laird, P.W.; Radenbaugh, A.; Ma, S.; Stuart, J.M.; Averett Byers, L.; Baylin, S.B.; Govindan, R.; Meyerson, M.; Rosenberg, M.; Gabriel, S.B.; Cibulskis, K.; Sougnez, C.; Kim, J.; Stewart, C.; Lichtenstein, L.; Lander, E.S.; Lawrence, M.S.; Getz, Kandoth, C.; Fulton, R.; Fulton, L.L.; McLellan, M.D.; Wilson, R.K.; Ye, K.; Fronick, C.C.; Maher, C.A.; Miller, C.A.; Wendl, M.C.; Cabanski, C.; Ding, L.; Mardis, E.; Govindan, R.; Creighton, C.J.; Wheeler, D.; Balasundaram, M.; Butterfield, Y.S.; Carlsen, R.; Chu, A.; Chuah, E.; Dhalla, N.; Guin, R.; Hirst, C.; Lee, D.; Li, H.I.; Mayo, M.; Moore, R.A.; Mungall, A.J.; Schein, J.E.; Sipahimalani, P.; Tam, A.; Varhol, R.; Robertson, A.; Wye, N.; Thiessen, N.; Holt, R.A.; Jones, S.J.; Marra, M.A.; Campbell, J.D.; Brooks, A.N.; Chmielecki, J.; Imielinski, M.; Onofrio, R.C.; Hodis, E.; Zack, T.; Sougnez, C.; Helman, E.; Sekhar Pedamallu, C.; Mesirov, J.; Cherniack, A.D.; Saksena, G.; Schumacher, S.E.; Carter, S.L.; Hernandez, B.; Garraway, L.; Beroukhim, R.; Gabriel, S.B.; Getz, G.; Meyerson, M.; Hadjipanayis, A.; Lee, S.; Mahadeshwar, H.S.; Pantazi, A.; Protopopov, A.; Ren, X.; Seth, S.; Song, X.; Tang, J.; Yang, L.; Zhang, J.; Chen, P.C.; Parfenov, M.; Wei Xu, A.; Santoso, N.; Chin, L.; Park, P.J.; Kucherlapati, R.; Hoadley, K.A.; Auman, J.T.; Meng, S.; Shi, Y.; Buda, E.; Waring, S.; Veluvolu, U.; Tan, D.; Mieczkowski, P.A.; Jones, C.D.; Simons, J.V.; Soloway, M.G.; Bodenheimer, T.; Jefferys, S.R.; Roach, J.; Hoyle, A.P.; Wu, J.; Balu, S.; Singh, D.; Prins, J.F.; Marron, J.S.; Parker, J.S.; Hayes, D.N.; Perou, C.M.; Liu, J.; Cope, L.; Danilova, L.; Weisenberger, D.J.; Maglinte, D.T.; Lai, P.H.; Bootwalla, M.S.; Van Den Berg, D.J.; Triche, T. Jr; Baylin, S.B.; Laird, P.W.; Rosenberg, M.; Chin, L.; Zhang, J.; Cho, J.; DiCara, D.; Heiman, D.; Lin, P.; Mallard, W.; Voet, D.; Zhang, H.; Zou, L.; Noble, M.S.; Lawrence, M.S.; Saksena, G.; Gehlenborg, N.; Thorvaldsdottir, H.; Mesirov, J.; Nazaire, M.D.; Robinson, J.; Getz, G.; Lee, W.; Aksoy, B.A.; Ciriello, G.; Taylor, B.S.; Dresdner, G.; Gao, J.; Gross, B.; Seshan, V.E.; Ladanyi, M.; Reva, B.; Sinha, R.; Sumer, S.O.; Weinhold, N.; Schultz, N.; Shen, R.; Sander, C.; Ng, S.; Ma, S.; Zhu, J.; Radenbaugh, A.; Stuart, J.M.; Benz, C.C.; Yau, C.; Haussler, D.; Spellman, P.T.; Wilkerson, M.D.; Parker, J.S.; Hoadley, K.A.; Kimes, P.K.; Hayes, D.N.; Perou, C.M.; Broom, B.M.; Wang, J.; Lu, Y.; Kwok Shing Ng, P.; Diao, L.; Averett Byers, L.; Liu, W.; Heymach, J.V.; Amos, C.I.; Weinstein, J.N.; Akbani, R.; Mills, G.B.; Curley, E.; Paulauskis, J.; Lau, K.; Morris, S.; Shelton, T.; Mallery, D.; Gardner, J.; Penny, R.; Saller, C.; Tarvin, K.; Richards, W.G.; Cerfolio, R.; Bryant, A.; Raymond, D.P.; Pennell, N.A.; Farver, C.; Czerwinski, C.; Huelsenbeck-Dill, L.; Iacocca, M.; Petrelli, N.; Rabeno, B.; Brown, J.; Bauer, T.; Dolzhanskiy, O.; Potapova, O.; Rotin, D.; Voronina, O.; Nemirovich-Danchenko, E.; Fedosenko, K.V.; Gal, A.; Behera, M.; Ramalingam, S.S.; Sica, G.; Flieder, D.; Boyd, J.; Weaver, J.; Kohl, B.; Huy Quoc Thinh, D.; Sandusky, G.; Juhl, H.; Duhig, E.; Illei, P.; Gabrielson, E.; Shin, J.; Lee, B.; Rodgers, K.; Trusty, D.; Brock, M.V.; Williamson, C.; Burks, E.; Rieger-Christ, K.; Holway, A.; Sullivan, T.; Wigle, D.A.; Asiedu, M.K.; Kosari, F.; Travis, W.D.; Rekhtman, N.; Zakowski, M.; Rusch, V.W.; Zippile, P.; Suh, J.; Pass, H.; Goparaju, C.; Owusu-Sarpong, Y.; Bartlett, J.M.; Kodeeswaran, S.; Parfitt, J.; Sekhon, H.; Albert, M.; Eckman, J.; Myers, J.B.; Cheney, R.; Morrison, C.; Gaudioso, C.; Borgia, J.A.; Bonomi, P.; Pool, M.; Liptay, M.J.; Moiseenko, F.; Zaytseva, I.; Dienemann, H.; Meister, M.; Schnabel, P.A.; Muley, T.R.; Peifer, M.; Gomez-Fernandez, C.; Herbert, L.; Egea, S.; Huang, M.; Thorne, L.B.; Boice, L.; Hill Salazar, A.; Funkhouser, W.K.; Rathmell, W.K.; Dhir, R.; Yousem, S.A.; Dacic, S.; Schneider, F.; Siegfried, J.M.; Hajek, R.; Watson, M.A.; McDonald, S.; Meyers, B.; Clarke, B.; Yang, I.A.; Fong, K.M.; Hunter, L.; Windsor, M.; Bowman, R.V.; Peters, S.; Letovanec, I.; Khan, K.Z.; Jensen, M.A.; Snyder, E.E.; Srinivasan, D.; Kahn, A.B.; Baboud, J.; Pot, D.A.; Mills Shaw, K.R.; Sheth, M.; Davidsen, T.; Demchok, J.A.; Yang, L.; Wang, Z.; Tarnuzzer, R.; Zenklusen, J.C.; Ozenberger, B.A.; Sofia, H.J.; Travis, W.D.; Cheney, R.; Clarke, B.; Dacic, S.; Duhig, E.; Funkhouser, W.K.; Illei, P.; Farver, C.; Rekhtman, N.; Sica, G.; Suh, J.; Tsao, M.S.; Travis, W.D.; Cheney, R.; Clarke, B.; Dacic, S.; Duhig, E.; Funkhouser, W.K.; Illei, P.; Farver, C.; Rekhtman, N.; Sica, G.; Suh, J.; Tsao, M.S. Comprehensive molecular profiling of lung adenocarcinoma. Nature, 2014, 511(7511), 543-550.
Ding, L.; Getz, G.; Wheeler, D.A.; Mardis, E.R.; McLellan, M.D.; Cibulskis, K.; Sougnez, C.; Greulich, H.; Muzny, D.M.; Morgan, M.B.; Fulton, L.; Fulton, R.S.; Zhang, Q.; Wendl, M.C.; Lawrence, M.S.; Larson, D.E.; Chen, K.; Dooling, D.J.; Sabo, A.; Hawes, A.C.; Shen, H.; Jhangiani, S.N.; Lewis, L.R.; Hall, O.; Zhu, Y.; Mathew, T.; Ren, Y.; Yao, J.; Scherer, S.E.; Clerc, K.; Metcalf, G.A.; Ng, B.; Milosavljevic, A.; Gonzalez-Garay, M.L.; Osborne, J.R.; Meyer, R.; Shi, X.; Tang, Y.; Koboldt, D.C.; Lin, L.; Abbott, R.; Miner, T.L.; Pohl, C.; Fewell, G.; Haipek, C.; Schmidt, H.; Dunford-Shore, B.H.; Kraja, A.; Crosby, S.D.; Sawyer, C.S.; Vickery, T.; Sander, S.; Robinson, J.; Winckler, W.; Baldwin, J.; Chirieac, L.R.; Dutt, A.; Fennell, T.; Hanna, M.; Johnson, B.E.; Onofrio, R.C.; Thomas, R.K.; Tonon, G.; Weir, B.A.; Zhao, X.; Ziaugra, L.; Zody, M.C.; Giordano, T.; Orringer, M.B.; Roth, J.A.; Spitz, M.R.; Wistuba, I.I.; Ozenberger, B.; Good, P.J.; Chang, A.C.; Beer, D.G.; Watson, M.A.; Ladanyi, M.; Broderick, S.; Yoshizawa, A.; Travis, W.D.; Pao, W.; Province, M.A.; Weinstock, G.M.; Varmus, H.E.; Gabriel, S.B.; Lander, E.S.; Gibbs, R.A.; Meyerson, M.; Wilson, R.K. Somatic mutations affect key pathways in lung adenocarcinoma. Nature, 2008, 455(7216), 1069-1075.
[] [PMID: 18948947]
Jordan, E.J.; Kim, H.R.; Arcila, M.E.; Barron, D.; Chakravarty, D.; Gao, J.; Chang, M.T.; Ni, A.; Kundra, R.; Jonsson, P.; Jayakumaran, G.; Gao, S.P.; Johnsen, H.C.; Hanrahan, A.J.; Zehir, A.; Rekhtman, N.; Ginsberg, M.S.; Li, B.T.; Yu, H.A.; Paik, P.K.; Drilon, A.; Hellmann, M.D.; Reales, D.N.; Benayed, R.; Rusch, V.W.; Kris, M.G.; Chaft, J.E.; Baselga, J.; Taylor, B.S.; Schultz, N.; Rudin, C.M.; Hyman, D.M.; Berger, M.F.; Solit, D.B.; Ladanyi, M.; Riely, G.J. Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies. Cancer Discov., 2017, 7(6), 596-609.
[] [PMID: 28336552]
Rizvi, H.; Sanchez-Vega, F.; La, K.; Chatila, W.; Jonsson, P.; Halpenny, D.; Plodkowski, A.; Long, N.; Sauter, J.L.; Rekhtman, N.; Hollmann, T.; Schalper, K.A.; Gainor, J.F.; Shen, R.; Ni, A.; Arbour, K.C.; Merghoub, T.; Wolchok, J.; Snyder, A.; Chaft, J.E.; Kris, M.G.; Rudin, C.M.; Socci, N.D.; Berger, M.F.; Taylor, B.S.; Zehir, A.; Solit, D.B.; Arcila, M.E.; Ladanyi, M.; Riely, G.J.; Schultz, N.; Hellmann, M.D. Molecular determinants of response to anti-programmed cell death (pd)-1 and anti-programmed death-ligand (pd-l)-ligand 1 blockade in patients with non-small-cell lung cancer profiled with targeted next-generation sequencing. J. Clin. Oncol., 2018, 36(7), 633-641.
[] [PMID: 29337640]
Campbell, J.D.; Alexandrov, A.; Kim, J.; Wala, J.; Berger, A.H.; Pedamallu, C.S.; Shukla, S.A.; Guo, G.; Brooks, A.N.; Murray, B.A.; Imielinski, M.; Hu, X.; Ling, S.; Akbani, R.; Rosenberg, M.; Cibulskis, C.; Ramachandran, A.; Collisson, E.A.; Kwiatkowski, D.J.; Lawrence, M.S.; Weinstein, J.N.; Verhaak, R.G.; Wu, C.J.; Hammerman, P.S.; Cherniack, A.D.; Getz, G.; Artyomov, M.N.; Schreiber, R.; Govindan, R.; Meyerson, M. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas. Nat. Genet., 2016, 48(6), 607-616.
[] [PMID: 27158780]
Hammerman, P.S.; Lawrence, M.S.; Voet, D.; Jing, R.; Cibulskis, K.; Sivachenko, A.; Stojanov, P.; Mckenna, A.; Lander, E.S.; Gabriel, S. Comprehensive genomic characterization of squamous cell lung cancers. Nature, 2012, 489(7417), 519-525.
[] [PMID: 22960745]
Demierre, M-F.; Higgins, P.D.R.; Gruber, S.B.; Hawk, E.; Lippman, S.M. Statins and cancer prevention. Nat. Rev. Cancer, 2005, 5(12), 930-942.
[] [PMID: 16341084]
Khurana, V.; Bejjanki, H.R.; Caldito, G.; Owens, M.W. Statins reduce the risk of lung cancer in humans: A large case-control study of US veterans. Chest, 2007, 131(5), 1282-1288.
[] [PMID: 17494779]
Hung, M-S.; Chen, I.C.; Lee, C-P.; Huang, R-J.; Chen, P-C.; Tsai, Y-H.; Yang, Y-H. Statin improves survival in patients with EGFR-TKI lung cancer: A nationwide population-based study. PLoS One, 2017, 12(2), e0171137-e0171137.
[] [PMID: 28158206]
Ukomadu, C.; Dutta, A. p21-dependent inhibition of colon cancer cell growth by mevastatin is independent of inhibition of G1 cyclin-dependent kinases. J. Biol. Chem., 2003, 278(44), 43586-43594.
[] [PMID: 12930830]
Yang, Z.; Su, Z.; DeWitt, J.P.; Xie, L.; Chen, Y.; Li, X.; Han, L.; Li, D.; Xia, J.; Zhang, Y.; Yang, Y.; Jin, C.; Zhang, J.; Li, S.; Li, K.; Zhang, Z.; Qu, X.; He, Z.; Chen, Y.; Shen, Y.; Ren, M.; Yuan, Z. Fluvastatin prevents lung adenocarcinoma bone metastasis by triggering autophagy. EBioMedicine, 2017, 19, 49-59.
[] [PMID: 28454732]
Kris, M.G.; Johnson, B.E.; Berry, L.D.; Kwiatkowski, D.J.; Iafrate, A.J.; Wistuba, I.I.; Varella-Garcia, M.; Franklin, W.A.; Aronson, S.L.; Su, P.F.; Shyr, Y.; Camidge, D.R.; Sequist, L.V.; Glisson, B.S.; Khuri, F.R.; Garon, E.B.; Pao, W.; Rudin, C.; Schiller, J.; Haura, E.B.; Socinski, M.; Shirai, K.; Chen, H.; Giaccone, G.; Ladanyi, M.; Kugler, K.; Minna, J.D.; Bunn, P.A. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA, 2014, 311(19), 1998-2006.
[] [PMID: 24846037]
Turrell, F.K.; Kerr, E.M.; Gao, M.; Thorpe, H.; Doherty, G.J.; Cridge, J.; Shorthouse, D.; Speed, A.; Samarajiwa, S.; Hall, B.A.; Griffiths, M.; Martins, C.P. Lung tumors with distinct p53 mutations respond similarly to p53 targeted therapy but exhibit genotype-specific statin sensitivity. Genes Dev., 2017, 31(13), 1339-1353.
[] [PMID: 28790158]
Kandoth, C.; McLellan, M.D.; Vandin, F.; Ye, K.; Niu, B.; Lu, C.; Xie, M.; Zhang, Q.; McMichael, J.F.; Wyczalkowski, M.A.; Leiserson, M.D.M.; Miller, C.A.; Welch, J.S.; Walter, M.J.; Wendl, M.C.; Ley, T.J.; Wilson, R.K.; Raphael, B.J.; Ding, L. Mutational landscape and significance across 12 major cancer types. Nature, 2013, 502(7471), 333-339.
[] [PMID: 24132290]
Peifer, M.; Fernández-Cuesta, L.; Sos, M.L.; George, J.; Seidel, D.; Kasper, L.H.; Plenker, D.; Leenders, F.; Sun, R.; Zander, T.; Menon, R.; Koker, M.; Dahmen, I.; Müller, C.; Di Cerbo, V.; Schildhaus, H.U.; Altmüller, J.; Baessmann, I.; Becker, C.; de Wilde, B.; Vandesompele, J.; Böhm, D.; Ansén, S.; Gabler, F.; Wilkening, I.; Heynck, S.; Heuckmann, J.M.; Lu, X.; Carter, S.L.; Cibulskis, K.; Banerji, S.; Getz, G.; Park, K.S.; Rauh, D.; Grütter, C.; Fischer, M.; Pasqualucci, L.; Wright, G.; Wainer, Z.; Russell, P.; Petersen, I.; Chen, Y.; Stoelben, E.; Ludwig, C.; Schnabel, P.; Hoffmann, H.; Muley, T.; Brockmann, M.; Engel-Riedel, W.; Muscarella, L.A.; Fazio, V.M.; Groen, H.; Timens, W.; Sietsma, H.; Thunnissen, E.; Smit, E.; Heideman, D.A.; Snijders, P.J.; Cappuzzo, F.; Ligorio, C.; Damiani, S.; Field, J.; Solberg, S.; Brustugun, O.T.; Lund-Iversen, M.; Sänger, J.; Clement, J.H.; Soltermann, A.; Moch, H.; Weder, W.; Solomon, B.; Soria, J.C.; Validire, P.; Besse, B.; Brambilla, E.; Brambilla, C.; Lantuejoul, S.; Lorimier, P.; Schneider, P.M.; Hallek, M.; Pao, W.; Meyerson, M.; Sage, J.; Shendure, J.; Schneider, R.; Büttner, R.; Wolf, J.; Nürnberg, P.; Perner, S.; Heukamp, L.C.; Brindle, P.K.; Haas, S.; Thomas, R.K. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat. Genet., 2012, 44(10), 1104-1110.
[] [PMID: 22941188]
The Cancer Genome Atlas, Koboldt, D.C.; Fulton, R.S.; McLellan, M.D.; Schmidt, H.; Kalicki-Veizer, J.; McMichael, J.F.; Fulton, L.L.; Dooling, D.J.; Ding, L.; Mardis, E.R.; Wilson, R.K.; Ally, A.; Balasundaram, M.; Butterfield, Y.S.; Carlsen, R.; Carter, C.; Chu, A.; Chuah, E.; Chun, H.J.; Coope, R.J.; Dhalla, N.; Guin, R.; Hirst, C.; Hirst, M.; Holt, R.A.; Lee, D.; Li, H.I.; Mayo, M.; Moore, R.A.; Mungall, A.J.; Pleasance, E.; Robertson, A.; Schein, J.E.; Shafiei, A.; Sipahimalani, P.; Slobodan, J.R.; Stoll, D.; Tam, A.; Thiessen, N.; Varhol, R.J.; Wye, N.; Zeng, T.; Zhao, Y.; Birol, I.; Jones, S.J.; Marra, M.A.; Cherniack, A.D.; Saksena, G.; Onofrio, R.C.; Pho, N.H.; Carter, S.L.; Schumacher, S.E.; Tabak, B.; Hernandez, B.; Gentry, J.; Nguyen, H.; Crenshaw, A.; Ardlie, K.; Beroukhim, R.; Winckler, W.; Getz, G.; Gabriel, S.B.; Meyerson, M.; Chin, L.; Park, P.J.; Kucherlapati, R.; Hoadley, K.A.; Auman, J.; Fan, C.; Turman, Y.J.; Shi, Y.; Li, L.; Topal, M.D.; He, X.; Chao, H.H.; Prat, A.; Silva, G.O.; Iglesia, M.D.; Zhao, W.; Usary, J.; Berg, J.S.; Adams, M.; Booker, J.; Wu, J.; Gulabani, A.; Bodenheimer, T.; Hoyle, A.P.; Simons, J.V.; Soloway, M.G.; Mose, L.E.; Jefferys, S.R.; Balu, S.; Parker, J.S.; Hayes, D.; Perou, C.M.; Malik, S.; Mahurkar, S.; Shen, H.; Weisenberger, D.J.; Triche, T. Jr; Lai, P.H.; Bootwalla, M.S.; Maglinte, D.T.; Berman, B.P.; Van Den Berg, D.J.; Baylin, S.B.; Laird, P.W.; Creighton, C.J.; Donehower, L.A.; Getz, G.; Noble, M.; Voet, D.; Saksena, G.; Gehlenborg, N.; DiCara, D.; Zhang, J.; Zhang, H.; Wu, C.J.; Liu, S.Y.; Lawrence, M.S.; Zou, L.; Sivachenko, A.; Lin, P.; Stojanov, P.; Jing, R.; Cho, J.; Sinha, R.; Park, R.W.; Nazaire, M.D.; Robinson, J.; Thorvaldsdottir, H.; Mesirov, J.; Park, P.J.; Chin, L.; Reynolds, S.; Kreisberg, R.B.; Bernard, B.; Bressler, R.; Erkkila, T.; Lin, J.; Thorsson, V.; Zhang, W.; Shmulevich, I.; Ciriello, G.; Weinhold, N.; Schultz, N.; Gao, J.; Cerami, E.; Gross, B.; Jacobsen, A.; Sinha, R.; Aksoy, B.; Antipin, Y.; Reva, B.; Shen, R.; Taylor, B.S.; Ladanyi, M.; Sander, C.; Anur, P.; Spellman, P.T.; Lu, Y.; Liu, W.; Verhaak, R.R.; Mills, G.B.; Akbani, R.; Zhang, N.; Broom, B.M.; Casasent, T.D.; Wakefield, C.; Unruh, A.K.; Baggerly, K.; Coombes, K.; Weinstein, J.N.; Haussler, D.; Benz, C.C.; Stuart, J.M.; Benz, S.C.; Zhu, J.; Szeto, C.C.; Scott, G.K.; Yau, C.; Paull, E.O.; Carlin, D.; Wong, C.; Sokolov, A.; Thusberg, J.; Mooney, S.; Ng, S.; Goldstein, T.C.; Ellrott, K.; Grifford, M.; Wilks, C.; Ma, S.; Craft, B.; Yan, C.; Hu, Y.; Meerzaman, D.; Gastier-Foster, J.M.; Bowen, J.; Ramirez, N.C.; Black, A.D.; Pyatt, R.E.; White, P.; Zmuda, E.J.; Frick, J.; Lichtenberg, T.M.; Brookens, R.; George, M.M.; Gerken, M.A.; Harper, H.A.; Leraas, K.M.; Wise, L.J.; Tabler, T.R.; McAllister, C.; Barr, T.; Hart-Kothari, M.; Tarvin, K.; Saller, C.; Sandusky, G.; Mitchell, C.; Iacocca, M.V.; Brown, J.; Rabeno, B.; Czerwinski, C.; Petrelli, N.; Dolzhansky, O.; Abramov, M.; Voronina, O.; Potapova, O.; Marks, J.R.; Suchorska, W.M.; Murawa, D.; Kycler, W.; Ibbs, M.; Korski, K.; Spychała, A.; Murawa, P.; Brzeziński, J.J.; Perz, H.; Łaźniak, R.; Teresiak, M.; Tatka, H.; Leporowska, E.; Bogusz-Czerniewicz, M.; Malicki, J.; Mackiewicz, A.; Wiznerowicz, M.; Le, X.V.; Kohl, B.; Nguyen, V.T.; Thorp, R.; Nguyen, V.B.; Sussman, H.; Bui, D.P.; Hajek, R.; Nguyen, P.H.; Tran, V.T.; Huynh, Q.T.; Khan, K.Z.; Penny, R.; Mallery, D.; Curley, E.; Shelton, C.; Yena, P.; Ingle, J.N.; Couch, F.J.; Lingle, W.L.; King, T.A.; Gonzalez-Angulo, A.M.; Mills, G.B.; Dyer, M.D.; Liu, S.; Meng, X.; Patangan, M.; Waldman, F.; Stöppler, H.; Rathmell, W.; Thorne, L.; Huang, M.; Boice, L.; Hill, A.; Morrison, C.; Gaudioso, C.; Bshara, W.; Daily, K.; Egea, S.C.; Pegram, M.; Gomez- Fernandez, C.; Dhir, R.; Bhargava, R.; Brufsky, A.; Shriver, C.D.; Hooke, J.A.; Campbell, J.L.; Mural, R.J.; Hu, H.; Somiari, S.; Larson, C.; Deyarmin, B.; Kvecher, L.; Kovatich, A.J.; Ellis, M.J.; King, T.A.; Hu, H.; Couch, F.J.; Mural, R.J.; Stricker, T.; White, K.; Olopade, O.; Ingle, J.N.; Luo, C.; Chen, Y.; Marks, J.R.; Waldman, F.; Wiznerowicz, M.; Bose, R.; Chang, L.W.; Beck, A.H.; Gonzalez- Angulo, A.M.; Pihl, T.; Jensen, M.; Sfeir, R.; Kahn, A.; Chu, A.; Kothiyal, P.; Wang, Z.; Snyder, E.; Pontius, J.; Ayala, B.; Backus, M.; Walton, J.; Baboud, J.; Berton, D.; Nicholls, M.; Srinivasan, D.; Raman, R.; Girshik, S.; Kigonya, P.; Alonso, S.; Sanbhadti, R.; Barletta, S.; Pot, D.; Sheth, M.; Demchok, J.A.; Shaw, K.R.; Yang, L.; Eley, G.; Ferguson, M.L.; Tarnuzzer, R.W.; Zhang, J.; Dillon, L.A.; Buetow, K.; Fielding, P.; Ozenberger, B.A.; Guyer, M.S.; Sofia, H.J.; Palchik, J.D. Comprehensive molecular portraits of human breast tumours. Nature, 2012, 490(7418), 61-70.
[] [PMID: 23000897]
The Cancer Genome Atlas Research, Bell, D.; Berchuck, A.; Birrer, M.; Chien, J.; Cramer, D.; Dao, F.; Dhir, R.; DiSaia, P.; Gabra, H.; Glenn, P.; Godwin, A.; Gross, J.; Hartmann, L.; Huang, M.; Huntsman, D.; Iacocca, M.; Imielinski, M.; Kalloger, S.; Karlan, B.; Levine, D.; Mills, G.; Morrison, C.; Mutch, D.; Olvera, N.; Orsulic, S.; Park, K.; Petrelli, N.; Rabeno, B.; Rader, J.; Sikic, B.; Smith- McCune, K.; Sood, A.; Bowtell, D.; Penny, R.; Testa, J.; Chang, K.; Dinh, H.; Drummond, J.; Fowler, G.; Gunaratne, P.; Hawes, A.; Kovar, C.; Lewis, L.; Morgan, M.; Newsham, I.; Santibanez, J.; Reid, J.; Trevino, L.; Wu, Y.; Wang, M.; Muzny, D.; Wheeler, D.; Gibbs, R.; Getz, G.; Lawrence, M.; Cibulskis, K.; Sivachenko, A.; Sougnez, C.; Voet, D.; Wilkinson, J.; Bloom, T.; Ardlie, K.; Fennell, T.; Baldwin, J.; Gabriel, S.; Lander, E.; Ding, L.L.; Fulton, R.; Koboldt, D.; McLellan, M.; Wylie, T.; Walker, J.; O'Laughlin, M.; Dooling, D.; Fulton, L.; Abbott, R.; Dees, N.; Zhang, Q.; Kandoth, C.; Wendl, M.; Schierding, W.; Shen, D.; Harris, C.; Schmidt, H.; Kalicki, J.; Delehaunty, K.; Fronick, C.; Demeter, R.; Cook, L.; Wallis, J.; Lin, L.; Magrini, V.; Hodges, J.; Eldred, J.; Smith, S.; Pohl, C.; Vandin, F.; Raphael, B.; Weinstock, G.; Mardis, E.; Wilson, R.; Meyerson, M.; Winckler, W.; Getz, G.; Verhaak, R.; Carter, S.; Mermel, C.; Saksena, G.; Nguyen, H.; Onofrio, R.; Lawrence, M.; Hubbard, D.; Gupta, S.; Crenshaw, A.; Ramos, A.; Ardlie, K.; Chin, L.; Protopopov, A.; Zhang, J.; Kim, T.; Perna, I.; Xiao, Y.; Zhang, H.; Ren, G.; Sathiamoorthy, N.; Park, R.; Lee, E.; Park, P.; Kucherlapati, R.; Absher, M.; Waite, L.; Sherlock, G.; Brooks, J.; Li, J.; Xu, J.; Myers, R.; Laird, P.W.; Cope, L.; Herman, J.; Shen, H.; Weisenberger, D.; Noushmehr, H.; Pan, F.; Triche, T. Jr; Berman, B.; Van Den Berg, D.; Buckley, J.; Baylin, S.; Spellman, P.; Purdom, E.; Neuvial, P.; Bengtsson, H.; Jakkula, L.; Durinck, S.; Han, J.; Dorton, S.; Marr, H.; Choi, Y.; Wang, V.; Wang, N.; Ngai, J.; Conboy, J.; Parvin, B.; Feiler, H.; Speed, T.; Gray, J.; Levine, A.; Socci, N.; Liang, Y.; Taylor, B.; Schultz, N.; Borsu, L.; Lash, A.; Brennan, C.; Viale, A.; Sander, C.; Ladanyi, M.; Hoadley, K.; Meng, S.; Du, Y.; Shi, Y.; Li, L.; Turman, Y.; Zang, D.; Helms, E.; Balu, S.; Zhou, X.; Wu, J.; Topal, M.; Hayes, D.; Perou, C.; Getz, G.; Voet, D.; Saksena, G.; Zhang, J.; Zhang, H.; Wu, C.; Shukla, S.; Cibulskis, K.; Lawrence, M.; Sivachenko, A.; Jing, R.; Park, R.; Liu, Y.; Park, P.; Noble, M.; Chin, L.; Carter, H.; Kim, D.; Karchin, R.; Spellman, P.; Purdom, E.; Neuvial, P.; Bengtsson, H.; Durinck, S.; Han, J.; Korkola, J.; Heiser, L.; Cho, R.; Hu, Z.; Parvin, B.; Speed, T.; Gray, J.; Schultz, N.; Cerami, E.; Taylor, B.; Olshen, A.; Reva, B.; Antipin, Y.; Shen, R.; Mankoo, P.; Sheridan, R.; Ciriello, G.; Chang, W.; Bernanke, J.; Borsu, L.; Levine, D.; Ladanyi, M.; Sander, C.; Haussler, D.; Benz, C.; Stuart, J.; Benz, S.; Sanborn, J.; Vaske, C.; Zhu, J.; Szeto, C.; Scott, G.; Yau, C.; Hoadley, K.; Du, Y.; Balu, S.; Hayes, D.; Perou, C.; Wilkerson, M.; Zhang, N.; Akbani, R.; Baggerly, K.; Yung, W.; Mills, G.; Weinstein, J.; Penny, R.; Shelton, T.; Grimm, D.; Hatfield, M.; Morris, S.; Yena, P.; Rhodes, P.; Sherman, M.; Paulauskis, J.; Millis, S.; Kahn, A.; Greene, J.; Sfeir, R.; Jensen, M.; Chen, J.; Whitmore, J.; Alonso, S.; Jordan, J.; Chu, A.; Zhang, J.; Barker, A.; Compton, C.; Eley, G.; Ferguson, M.; Fielding, P.; Gerhard, D.; Myles, R.; Schaefer, C.; Mills Shaw, K.; Vaught, J.; Vockley, J.; Good, P.; Guyer, M.; Ozenberger, B.; Peterson, J.; Thomson, E. Integrated genomic analyses of ovarian carcinoma. Nature, 2011, 474(7353), 609-615.
Song, Y.; Li, L.; Ou, Y.; Gao, Z.; Li, E.; Li, X.; Zhang, W.; Wang, J.; Xu, L.; Zhou, Y.; Ma, X.; Liu, L.; Zhao, Z.; Huang, X.; Fan, J.; Dong, L.; Chen, G.; Ma, L.; Yang, J.; Chen, L.; He, M.; Li, M.; Zhuang, X.; Huang, K.; Qiu, K.; Yin, G.; Guo, G.; Feng, Q.; Chen, P.; Wu, Z.; Wu, J.; Ma, L.; Zhao, J.; Luo, L.; Fu, M.; Xu, B.; Chen, B.; Li, Y.; Tong, T.; Wang, M.; Liu, Z.; Lin, D.; Zhang, X.; Yang, H.; Wang, J.; Zhan, Q. Identification of genomic alterations in oesophageal squamous cell cancer. Nature, 2014, 509(7498), 91-95.
[] [PMID: 24670651]
Filipczak, P.T.; Leng, S.; Tellez, C.S.; Do, K.C.; Grimes, M.J.; Thomas, C.L.; Walton-Filipczak, S.R.; Picchi, M.A.; Belinsky, S.A. P53-suppressed oncogene tet1 prevents cellular aging in lung cancer. Cancer Res., 2019, 79(8), 1758-1768.
[] [PMID: 30622117]
Mitsudomi, T.; Hamajima, N.; Ogawa, M.; Takahashi, T. Prognostic significance of p53 alterations in patients with non-small cell lung cancer: A meta-analysis. Clin. Cancer Res., 2000, 6(10), 4055-4063.
[PMID: 11051256]
Duffy, M.J.; Synnott, N.C.; Crown, J. Mutant p53 as a target for cancer treatment. Eur. J. Cancer, 2017, 83, 258-265.
[] [PMID: 28756138]
Lafky, J.M.; Wilken, J.A.; Baron, A.T.; Maihle, N.J. Clinical implications of the ErbB/Epidermal Growth Factor (EGF) receptor family and its ligands in ovarian cancer. Biochim. Biophys. Acta, 2008, 1785(2), 232-265.
[PMID: 18291115]
Lee, J.C.; Vivanco, I.; Beroukhim, R.; Huang, J.H.Y.; Feng, W.L.; DeBiasi, R.M.; Yoshimoto, K.; King, J.C.; Nghiemphu, P.; Yuza, Y.; Xu, Q.; Greulich, H.; Thomas, R.K.; Paez, J.G.; Peck, T.C.; Linhart, D.J.; Glatt, K.A.; Getz, G.; Onofrio, R.; Ziaugra, L.; Levine, R.L.; Gabriel, S.; Kawaguchi, T.; O’Neill, K.; Khan, H.; Liau, L.M.; Nelson, S.F.; Rao, P.N.; Mischel, P.; Pieper, R.O.; Cloughesy, T.; Leahy, D.J.; Sellers, W.R.; Sawyers, C.L.; Meyerson, M.; Mellinghoff, I.K. Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain. PLoS Med., 2006, 3(12), e485-e485.
[] [PMID: 17177598]
Paez, J.G.; Jänne, P.A.; Lee, J.C.; Tracy, S.; Greulich, H.; Gabriel, S.; Herman, P.; Kaye, F.J.; Lindeman, N.; Boggon, T.J.; Naoki, K.; Sasaki, H.; Fujii, Y.; Eck, M.J.; Sellers, W.R.; Johnson, B.E.; Meyerson, M. EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science, 2004, 304(5676), 1497-1500.
[] [PMID: 15118125]
Veale, D.; Kerr, N.; Gibson, G.J.; Kelly, P.J.; Harris, A.L. The relationship of quantitative epidermal growth factor receptor expression in non-small cell lung cancer to long term survival. Br. J. Cancer, 1993, 68(1), 162-165.
[] [PMID: 8391303]
Lynch, T.J.; Bell, D.W.; Sordella, R.; Gurubhagavatula, S.; Okimoto, R.A.; Brannigan, B.W.; Harris, P.L.; Haserlat, S.M.; Supko, J.G.; Haluska, F.G.; Louis, D.N.; Christiani, D.C.; Settleman, J.; Haber, D.A. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med., 2004, 350(21), 2129-2139.
[] [PMID: 15118073]
Yarden, Y.; Pines, G. The ERBB network: At last, cancer therapy meets systems biology. Nat. Rev. Cancer, 2012, 12(8), 553-563.
[] [PMID: 22785351]
Zhou, C.; Wu, Y.L.; Chen, G.; Feng, J.; Liu, X.Q.; Wang, C.; Zhang, S.; Wang, J.; Zhou, S.; Ren, S.; Lu, S.; Zhang, L.; Hu, C.; Hu, C.; Luo, Y.; Chen, L.; Ye, M.; Huang, J.; Zhi, X.; Zhang, Y.; Xiu, Q.; Ma, J.; Zhang, L.; You, C. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol., 2011, 12(8), 735-742.
[] [PMID: 21783417]
Mayekar, M.K.; Bivona, T.G. Current landscape of targeted therapy in lung cancer. Clin. Pharmacol. Ther., 2017, 102(5), 757-764.
[] [PMID: 28786099]

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