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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Review Article

Repurposing Drugs for Skin Cancer

Author(s): Levon M. Khachigian*

Volume 27, Issue 42, 2020

Page: [7214 - 7221] Pages: 8

DOI: 10.2174/0929867327666191220103901

Price: $65

Abstract

Drug repurposing is the process of developing existing or abandoned drugs for a different disease. Repurposing can circumvent higher costs and times associated with conventional drug discovery strategies because toxicity and pharmacokinetics profiles are typically already established. This brief review focuses on efforts to repurpose drugs for skin cancer and includes reuse of antihypertensives, anthelmintics and antifungals among a range of other medicines. Repurposing not only ushers promising known drugs for new indications, the process of repurposing can uncover new mechanistic insights in the pathogenesis of disease and uncover new opportunities for pharmaceutical intervention.

Keywords: Drug repurposing, drug repositioning, melanoma, skin cancer, cancer, disease, melanoma.

« Previous Next »
[1]
World Health Organization Cancer Today. International agency for research on cancer., Available at http://gco.iarc.fr/today/home (Accessed Date: 16th January, 2020)
[2]
Cancer Australia. cancer in Australia statistics. International Agency for Research on Cancer. Available at https://canceraustralia.gov.au/affected-cancer/what-cancer/cancer-australia-statistics (Accessed Date: 16th January, 2020)
[3]
International agency for research on cancer. World Cancer Report; World Health Organization: Lyon, France, 2014.
[4]
Burki, T.K. Oncology drug market worth predicted to increase. Lancet Oncol., 2015, 16(1)e10
[http://dx.doi.org/10.1016/S1470-2045(14)71164-7] [PMID: 25638545]
[5]
World health organization, skin cancers.. Available at https://www.who.int/uv/faq/skincancer/en/index1.html (Accessed Date: 16th January, 2020)
[6]
GLOBOCAN 2012: estimated cancer incidence, mortality and prevalence worldwide 2012. Available at https://publica-tions.iarc.fr/Databases/Iarc-Cancerbases/GLOBOCAN-2012-Estimated-Cancer-Incidence-Mortality-And-Prevalen-ce-Worldwide-In-2012-V1.0-2012 (Accessed Date: 16th January, 2020)
[7]
Cancer Council. Skin cancer., Available at https://www.cancer.org.au/cancer-information/types-of-cancer/skin-cancer (Accessed Date: 16th January, 2020)
[8]
Staples, M.P.; Elwood, M.; Burton, R.C.; Williams, J.L.; Marks, R.; Giles, G.G. Non-melanoma skin cancer in Australia: the 2002 national survey and trends since 1985. Med. J. Aust., 2006, 184(1), 6-10.
[http://dx.doi.org/10.5694/j.1326-5377.2006.tb00086.x] [PMID: 16398622]
[9]
Cancer Australia. Melanoma of the skin statistics. Available at https://melanoma.canceraustralia.gov.au/statistics (Accessed Date: 16th January, 2020)
[10]
Jenkins, R.W.; Barbie, D.A.; Flaherty, K.T. Mechanisms of resistance to immune checkpoint inhibitors. Br. J. Cancer, 2018, 118(1), 9-16.
[http://dx.doi.org/10.1038/bjc.2017.434] [PMID: 29319049]
[11]
Lim, S.Y.; Rizos, H. Immune cell profiling in the age of immune checkpoint inhibitors: implications for biomarker discovery and un-derstanding of resistance mechanisms. Mamm. Genome, 2018, 29(11-12), 866-878.
[http://dx.doi.org/10.1007/s00335-018-9757-4] [PMID: 29968076]
[12]
Shergold, A.L.; Millar, R.; Nibbs, R.J.B. Understanding and overcoming the resistance of cancer to PD-1/PD-L1 blockade. Pharmacol. Res., 2019, 145104258
[http://dx.doi.org/10.1016/j.phrs.2019.104258] [PMID: 31063806]
[13]
Lucena, S.R.; Salazar, N.; Gracia-Cazaña, T.; Zamarrón, A.; González, S.; Juarranz, Á.; Gilaberte, Y. Combined treatments with pho-todynamic therapy for non-melanoma skin cancer. Int. J. Mol. Sci., 2015, 16(10), 25912-25933.
[http://dx.doi.org/10.3390/ijms161025912] [PMID: 26516853]
[14]
Clark, C.M.; Furniss, M.; Mackay-Wiggan, J.M. Basal cell carcinoma: an evidence-based treatment update. Am. J. Clin. Dermatol., 2014, 15(3), 197-216.
[http://dx.doi.org/10.1007/s40257-014-0070-z] [PMID: 24733429]
[15]
Pushpakom, S.; Iorio, F.; Eyers, P.A.; Escott, K.J.; Hopper, S.; Wells, A.; Doig, A.; Guilliams, T.; Latimer, J.; McNamee, C.; Norris, A.; Sanseau, P.; Cavalla, D.; Pirmohamed, M. Drug repurposing: progress, challenges and recommendations. Nat. Rev. Drug Discov., 2019, 18(1), 41-58.
[http://dx.doi.org/10.1038/nrd.2018.168] [PMID: 30310233]
[16]
Pantziarka, P.; Verbaanderd, C.; Sukhatme, V.; Rica Capistrano, I.; Crispino, S.; Gyawali, B.; Rooman, I.; Van Nuffel, A.M.; Meheus, L.; Sukhatme, V.P.; Bouche, G. ReDO_DB: the repurposing drugs in oncology database. Ecancermedicalscience, 2018, 12, 886.
[http://dx.doi.org/10.3332/ecancer.2018.886] [PMID: 30679953]
[17]
Brown, A.S.; Patel, C.J. A standard database for drug repositioning. Sci. Data, 2017.4170029
[http://dx.doi.org/10.1038/sdata.2017.29] [PMID: 28291243]
[18]
Gns, H.S.; Gr, S.; Murahari, M.; Krishnamurthy, M. An update on drug repurposing: re-written saga of the drug’s fate. Biomed. Pharmacother., 2019, 110, 700-716.
[http://dx.doi.org/10.1016/j.biopha.2018.11.127] [PMID: 30553197]
[19]
Nowak-Sliwinska, P.; Scapozza, L.; Ruiz i Altaba, A.; Altaba, A. Drug repurposing in oncology: Compounds, pathways, phenotypes and computational approaches for colorectal cancer. Biochim. Biophys. Acta Rev. Cancer, 2019, 1871(2), 434-454.
[http://dx.doi.org/10.1016/j.bbcan.2019.04.005] [PMID: 31034926]
[20]
Australian Government. Ritauximab. The pharmaceutical benefits scheme. Available at https://www.pbs.gov.au/medicine/item/9544h-9611w (Accessed Date: 16th January, 2020)
[21]
Traish, A.M.; Melcangi, R.C.; Bortolato, M.; Garcia-Segura, L.M.; Zitzmann, M. Adverse effects of 5α-reductase inhibitors: what do we know, don’t know, and need to know? Rev. Endocr. Metab. Disord., 2015, 16(3), 177-198.
[http://dx.doi.org/10.1007/s11154-015-9319-y] [PMID: 26296373]
[22]
Friedman, B.; Cronstein, B. Methotrexate mechanism in treatment of rheumatoid arthritis. Joint Bone Spine, 2019, 86(3), 301-307.
[http://dx.doi.org/10.1016/j.jbspin.2018.07.004] [PMID: 30081197]
[23]
Colleoni, M.; Rocca, A.; Sandri, M.T.; Zorzino, L.; Masci, G.; Nolè, F.; Peruzzotti, G.; Robertson, C.; Orlando, L.; Cinieri, S. de, B.F.; Viale, G.; Goldhirsch, A. Low-dose oral methotrexate and cyclophosphamide in metastatic breast cancer: antitumor activity and correlation with vascular endothelial growth factor levels. Ann. Oncol., 2002, 13(1), 73-80.
[http://dx.doi.org/10.1093/annonc/mdf013] [PMID: 11863115]
[24]
Mangoni, A.A.; Tommasi, S.; Zinellu, A.; Sotgia, S.; Carru, C.; Piga, M.; Erre, G.L. Repurposing existing drugs for cardiovascular risk management: a focus on methotrexate. Drugs Context, 2018, 7212557
[http://dx.doi.org/10.7573/dic.212557] [PMID: 30459819]
[25]
Ridker, P.M.; Everett, B.M.; Pradhan, A.; MacFadyen, J.G.; Solomon, D.H.; Zaharris, E.; Mam, V.; Hasan, A.; Rosenberg, Y.; Itur-riaga, E.; Gupta, M.; Tsigoulis, M.; Verma, S.; Clearfield, M.; Libby, P.; Goldhaber, S.Z.; Seagle, R.; Ofori, C.; Saklayen, M.; Butman, S.; Singh, N.; Le May, M.; Bertrand, O.; Johnston, J.; Paynter, N.P.; Glynn, R.J.; Investigators, C. CIRT investigators. low-dose methotrexate for the prevention of atherosclerotic events. N. Engl. J. Med., 2019, 380(8), 752-762.
[http://dx.doi.org/10.1056/NEJMoa1809798] [PMID: 30415610]
[26]
Libby, P.; Ridker, P.M.; Hansson, G.K. Leducq transatlantic network on atherothrombosis. Inflammation in atherosclerosis: from pathophysiology to practice. J. Am. Coll. Cardiol., 2009, 54(23), 2129-2138.
[http://dx.doi.org/10.1016/j.jacc.2009.09.009] [PMID: 19942084]
[27]
Ridker, P.M.; Everett, B.M.; Thuren, T.; MacFadyen, J.G.; Chang, W.H.; Ballantyne, C.; Fonseca, F.; Nicolau, J.; Koenig, W.; Anker, S.D.; Kastelein, J.J.P.; Cornel, J.H.; Pais, P.; Pella, D.; Genest, J.; Cifkova, R.; Lorenzatti, A.; Forster, T.; Kobalava, Z.; Vida-Simiti, L.; Flather, M.; Shimokawa, H.; Ogawa, H.; Dellborg, M.; Rossi, P.R.F.; Troquay, R.P.T.; Libby, P.; Glynn, R.J.; Group, C.T. CANTOS trial group. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med., 2017, 377(12), 1119-1131.
[http://dx.doi.org/10.1056/NEJMoa1707914] [PMID: 28845751]
[28]
Crockett, S.D.; Schectman, R.; Stürmer, T.; Kappelman, M.D. Topiramate use does not reduce flares of inflammatory bowel disease. Dig. Dis. Sci., 2014, 59(7), 1535-1543.
[http://dx.doi.org/10.1007/s10620-014-3040-7] [PMID: 24504592]
[29]
Bharadwaj, P.R.; Bates, K.A.; Porter, T.; Teimouri, E.; Perry, G.; Steele, J.W.; Gandy, S.; Groth, D.; Martins, R.N.; Verdile, G. Latrepirdine: molecular mechanisms underlying potential therapeutic roles in Alzheimer’s and other neurodegenerative diseases. Transl. Psychiatry, 2013, 3(12)e332
[http://dx.doi.org/10.1038/tp.2013.97] [PMID: 24301650]
[30]
Ortiz, A.; Gui, J.; Zahedi, F.; Yu, P.; Cho, C.; Bhattacharya, S.; Carbone, C.J.; Yu, Q.; Katlinski, K.V.; Katlinskaya, Y.V.; Handa, S.; Haas, V.; Volk, S.W.; Brice, A.K.; Wals, K.; Matheson, N.J.; Antrobus, R.; Ludwig, S.; Whiteside, T.L.; Sander, C.; Tarhini, A.A.; Kirkwood, J.M.; Lehner, P.J.; Guo, W.; Rui, H.; Minn, A.J.; Koumenis, C.; Diehl, J.A.; Fuchs, S.Y. An Interferon-driven oxysterol-based defense against tumor-derived extracellular vesicles. Cancer Cell, 2019, 35(1), 33-45.e6.
[http://dx.doi.org/10.1016/j.ccell.2018.12.001] [PMID: 30645975]
[31]
He, X.; Wang, J.; Dou, J.; Yu, F.; Cai, K.; Li, X.; Zhang, H.; Gu, N. Antitumor efficacy induced by a B16F10 tumor cell vaccine treated with mitoxantrone alone or in combination with reserpine and verapamil in mice. Exp. Ther. Med., 2011, 2(5), 911-916.
[http://dx.doi.org/10.3892/etm.2011.283] [PMID: 22977597]
[32]
Perissin, L.; Rapozzi, V.; Zorzet, S.; Giraldi, T. Blockers of adrenergic neurons and receptors, tumor progression and effects of rotational stress in mice. Anticancer Res., 1996, 16(6B), 3409-3413.
[PMID: 9042199]
[33]
Riedel, T.; Demaria, O.; Zava, O.; Joncic, A.; Gilliet, M.; Dyson, P.J. Drug repurposing approach identifies a synergistic drug combi-nation of an antifungal agent and an experimental organometallic drug for melanoma treatment. Mol. Pharm., 2018, 15(1), 116-126.
[http://dx.doi.org/10.1021/acs.molpharmaceut.7b00764] [PMID: 29185769]
[34]
Trousil, S.; Chen, S.; Mu, C.; Shaw, F.M.; Yao, Z.; Ran, Y.; Shakuntala, T.; Merghoub, T.; Manstein, D.; Rosen, N.; Cantley, L.C.; Zippin, J.H.; Zheng, B. Phenformin enhances the efficacy of ERK inhibition in NF1-mutant melanoma. J. Invest. Dermatol., 2017, 137(5), 1135-1143.
[http://dx.doi.org/10.1016/j.jid.2017.01.013] [PMID: 28143781]
[35]
Petrachi, T.; Romagnani, A.; Albini, A.; Longo, C.; Argenziano, G.; Grisendi, G.; Dominici, M.; Ciarrocchi, A.; Dallaglio, K. Thera-peutic potential of the metabolic modulator phenformin in targeting the stem cell compartment in melanoma. Oncotarget, 2017, 8(4), 6914-6928.
[http://dx.doi.org/10.18632/oncotarget.14321] [PMID: 28036292]
[36]
Kim, S.H.; Li, M.; Trousil, S.; Zhang, Y.; Pasca di Magliano, M.; Swanson, K.D.; Zheng, B. Phenformin inhibits myeloid-derived suppressor cells and enhances the anti-tumor activity of PD-1 blockade in melanoma. J. Invest. Dermatol., 2017, 137(8), 1740-1748.
[http://dx.doi.org/10.1016/j.jid.2017.03.033] [PMID: 28433543]
[37]
Tripathi, R.; Fiore, L.S.; Richards, D.L.; Yang, Y.; Liu, J.; Wang, C.; Plattner, R. Abl and Arg mediate cysteine cathepsin secretion to facilitate melanoma invasion and metastasis. Sci. Signal., 2018, 11(518)eaao0422
[http://dx.doi.org/10.1126/scisignal.aao0422] [PMID: 29463776]
[38]
Guo, J.; Carvajal, R.D.; Dummer, R.; Hauschild, A.; Daud, A.; Bastian, B.C.; Markovic, S.N.; Queirolo, P.; Arance, A.; Berking, C.; Camargo, V.; Herchenhorn, D.; Petrella, T.M.; Schadendorf, D.; Sharfman, W.; Testori, A.; Novick, S.; Hertle, S.; Nourry, C.; Chen, Q.; Hodi, F.S. Efficacy and safety of nilotinib in patients with KIT-mutated metastatic or inoperable melanoma: final results from the global, single-arm, phase II TEAM trial. Ann. Oncol., 2017, 28(6), 1380-1387.
[http://dx.doi.org/10.1093/annonc/mdx079] [PMID: 28327988]
[39]
Delyon, J.; Chevret, S.; Jouary, T.; Dalac, S.; Dalle, S.; Guillot, B.; Arnault, J.P.; Avril, M.F.; Bedane, C.; Bens, G.; Pham-Ledard, A.; Mansard, S.; Grange, F.; Machet, L.; Meyer, N.; Legoupil, D.; Saiag, P.; Idir, Z.; Renault, V.; Deleuze, J.F.; Hindie, E.; Battistella, M.; Dumaz, N.; Mourah, S.; Lebbe, C. GCC (French group of skin cancer). STAT3 mediates nilotinib response in KIT-altered melanoma: a phase II multicenter trial of the french skin cancer network. J. Invest. Dermatol., 2018, 138(1), 58-67.
[http://dx.doi.org/10.1016/j.jid.2017.07.839] [PMID: 28843487]
[40]
Li, Y.; Acharya, G.; Elahy, M.; Xin, H.; Khachigian, L.M. The anthelmintic flubendazole blocks human melanoma growth and metastasis and suppresses programmed cell death protein-1 and myeloid-derived suppressor cell accumulation. Cancer Lett., 2019, 459, 268-276.
[http://dx.doi.org/10.1016/j.canlet.2019.05.026] [PMID: 31128215]
[41]
Oh, E.; Kim, Y.J.; An, H.; Sung, D.; Cho, T.M.; Farrand, L.; Jang, S.; Seo, J.H.; Kim, J.Y. Flubendazole elicits anti-metastatic effects in triple-negative breast cancer via STAT3 inhibition. Int. J. Cancer, 2018, 143(8), 1978-1993.
[http://dx.doi.org/10.1002/ijc.31585] [PMID: 29744876]
[42]
Hou, Z.J.; Luo, X.; Zhang, W.; Peng, F.; Cui, B.; Wu, S.J.; Zheng, F.M.; Xu, J.; Xu, L.Z.; Long, Z.J.; Wang, X.T.; Li, G.H.; Wan, X.Y.; Yang, Y.L.; Liu, Q. Flubendazole, FDA-approved anthelmintic, targets breast cancer stem-like cells. Oncotarget, 2015, 6(8), 6326-6340.
[http://dx.doi.org/10.18632/oncotarget.3436] [PMID: 25811972]
[43]
Zhou, X.; Liu, J.; Zhang, J.; Wei, Y.; Li, H. Flubendazole inhibits glioma proliferation by G2/M cell cycle arrest and pro-apoptosis. Cell Death Discov., 2018, 4, 18.
[http://dx.doi.org/10.1038/s41420-017-0017-2] [PMID: 29531815]
[44]
Spagnuolo, P.A.; Hu, J.; Hurren, R.; Wang, X.; Gronda, M.; Sukhai, M.A.; Di Meo, A.; Boss, J.; Ashali, I.; Beheshti Zavareh, R.; Fine, N.; Simpson, C.D.; Sharmeen, S.; Rottapel, R.; Schimmer, A.D. The antihelmintic flubendazole inhibits microtubule function through a mechanism distinct from Vinca alkaloids and displays preclinical activity in leukemia and myeloma. Blood, 2010, 115(23), 4824-4833.
[http://dx.doi.org/10.1182/blood-2009-09-243055] [PMID: 20348394]
[45]
Zhang, Q.L.; Lian, D.D.; Zhu, M.J.; Li, X.M.; Lee, J.K.; Yoon, T.J.; Lee, J.H.; Jiang, R.H.; Kim, C.D. Antitumor effect of albendazole on cutaneous squamous cell carcinoma (SCC) cells. BioMed Res. Int., 2019, 20193689517
[http://dx.doi.org/10.1155/2019/2076579] [PMID: 31281836]
[46]
Patel, K.; Doudican, N.A.; Schiff, P.B.; Orlow, S.J. Albendazole sensitizes cancer cells to ionizing radiation. Radiat. Oncol., 2011, 6, 160.
[http://dx.doi.org/10.1186/1748-717X-6-160] [PMID: 22094106]
[47]
Jacobson, M.K.; Jacobson, E.L. Vitamin B3 in health and disease: toward the second century of discovery. Methods Mol. Biol., 2018, 1813, 3-8.
[http://dx.doi.org/10.1007/978-1-4939-8588-3_1] [PMID: 30097857]
[48]
Chen, A.C.; Martin, A.J.; Choy, B.; Fernández-Peñas, P.; Dalziell, R.A.; McKenzie, C.A.; Scolyer, R.A.; Dhillon, H.M.; Vardy, J.L.; Kricker, A.; St George, G.; Chinniah, N.; Halliday, G.M.; Damian, D.L. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N. Engl. J. Med., 2015, 373(17), 1618-1626.
[http://dx.doi.org/10.1056/NEJMoa1506197] [PMID: 26488693]
[49]
Kim, D.J.; Kim, J.; Spaunhurst, K.; Montoya, J.; Khodosh, R.; Chandra, K.; Fu, T.; Gilliam, A.; Molgo, M.; Beachy, P.A.; Tang, J.Y. Open-label, exploratory phase II trial of oral itraconazole for the treatment of basal cell carcinoma. J. Clin. Oncol., 2014, 32(8), 745-751.
[http://dx.doi.org/10.1200/JCO.2013.49.9525] [PMID: 24493717]
[50]
Gailani, M.R.; Ståhle-Bäckdahl, M.; Leffell, D.J.; Glynn, M.; Zaphiropoulos, P.G.; Pressman, C.; Undén, A.B.; Dean, M.; Brash, D.E.; Bale, A.E.; Toftgård, R. The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nat. Genet., 1996, 14(1), 78-81.
[http://dx.doi.org/10.1038/ng0996-78] [PMID: 8782823]
[51]
Dahmane, N.; Lee, J.; Robins, P.; Heller, P.; Ruiz i Altaba, A. Activation of the transcription factor Gli1 and the Sonic hedgehog sig-nalling pathway in skin tumours. Nature, 1997, 389(6653), 876-881.
[http://dx.doi.org/10.1038/39918] [PMID: 9349822]
[52]
Xie, J.; Murone, M.; Luoh, S.M.; Ryan, A.; Gu, Q.; Zhang, C.; Bonifas, J.M.; Lam, C.W.; Hynes, M.; Goddard, A.; Rosenthal, A.; Epstein, E.H. Jr.; de Sauvage, F.J. Activating smoothened mutations in sporadic basal-cell carcinoma. Nature, 1998, 391(6662), 90-92.
[http://dx.doi.org/10.1038/34201] [PMID: 9422511]
[53]
Kim, J.; Tang, J.Y.; Gong, R.; Kim, J.; Lee, J.J.; Clemons, K.V.; Chong, C.R.; Chang, K.S.; Fereshteh, M.; Gardner, D.; Reya, T.; Liu, J.O.; Epstein, E.H.; Stevens, D.A.; Beachy, P.A. Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth. Cancer Cell, 2010, 17(4), 388-399.
[http://dx.doi.org/10.1016/j.ccr.2010.02.027] [PMID: 20385363]
[54]
Liang, G.; Liu, M.; Wang, Q.; Shen, Y.; Mei, H.; Li, D.; Liu, W. Itraconazole exerts its anti-melanoma effect by suppressing Hedgehog, Wnt, and PI3K/mTOR signaling pathways. Oncotarget, 2017, 8(17), 28510-28525.
[http://dx.doi.org/10.18632/oncotarget.15324] [PMID: 28212537]
[55]
Carbone, C.; Martins-Gomes, C.; Pepe, V.; Silva, A.M.; Musumeci, T.; Puglisi, G.; Furneri, P.M.; Souto, E.B. Repurposing itraconazole to the benefit of skin cancer treatment: A combined azole-DDAB nanoencapsulation strategy. Colloids Surf. B Biointerfaces, 2018, 167, 337-344.
[http://dx.doi.org/10.1016/j.colsurfb.2018.04.031] [PMID: 29684903]
[56]
Khosravi, A.; Jayaram, B.; Goliaei, B.; Masoudi-Nejad, A. Active repurposing of drug candidates for melanoma based on GWAS, PheWAS and a wide range of omics data. Mol. Med., 2019, 25(1), 30.
[http://dx.doi.org/10.1186/s10020-019-0098-x] [PMID: 31221082]
[57]
Han, Y.; Gu, Z.; Wu, J.; Huang, X.; Zhou, R.; Shi, C.; Tao, W.; Wang, L.; Wang, Y.; Zhou, G.; Li, J.; Zhang, Z.; Sun, S. Repurposing ponatinib as a potent agent against KIT mutant melanomas. Theranostics, 2019, 9(7), 1952-1964.
[http://dx.doi.org/10.7150/thno.30890] [PMID: 31037149]
[58]
National cancer institute.. Drugs approved for skin cancer. Available at: https://www.cancer.gov/about-cancer/treat-ment/drugs/skin (Accessed Date: 16th January, 2020)

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