Skip to main content
SpringerLink
Log in

Principles of Targeted Therapy

  • Living reference work entry
  • First Online:
Melanoma

  • 161 Accesses

Abstract

With the increasing volume of genetic melanoma profiling, key oncogenic driver mutations have attracted substantial attention as therapeutic targets. Chief among these are BRAF and KIT. Since BRAF mutations occur in about half of all melanomas, BRAF pathway inhibition has attracted the bulk of therapeutic attention. The discovery of BRAF mutations in cutaneous melanomas led to considerable research into the role of BRAF/MEK/ERK signaling and its role in melanomagenesis. In parallel, drug discovery efforts targeting BRAF, MEK, and ERK led to promising therapeutic candidates. Single-agent BRAF inhibitors showed strong efficacy in metastatic melanoma patients, effectively transforming the treatment for BRAF-mutant cutaneous melanoma patients. MEK inhibitors also showed efficacy as single agents, but the combination of BRAF and MEK inhibitors was clearly superior to either single-agent treatment. ERK inhibitors are currently undergoing clinical development. KIT mutations are primarily found in acral and mucosal melanomas, and several KIT inhibitors have been tested in KIT-mutant melanoma clinical trials; so far none have been approved by regulatory agencies. The challenge for KIT inhibitors may lie in the rarity and diversity of KIT genetic mutations. This chapter explores the biology of BRAF- and KIT-mutant melanoma cells and describes discovery of therapeutic candidates and reviews their role in clinical care.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Arafeh R, Qutob N, Emmanuel R, Keren-Paz A, Madore J, Elkahloun A, Wilmott JS, Gartner JJ, Di Pizio A, Winograd-Katz S, Sindiri S, Rotkopf R, Dutton-Regester K, Johansson P, Pritchard AL, Waddell N, Hill VK, Lin JC, Hevroni Y, Rosenberg SA, Khan J, Ben-Dor S, Niv MY, Ulitsky I, Mann GJ, Scolyer RA, Hayward NK, Samuels Y (2015) Recurrent inactivating RASA2 mutations in melanoma. Nat Genet 47(12):1408–1410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boiko AD, Razorenova OV, van de Rijn M, Swetter SM, Johnson DL, Ly DP, Butler PD, Yang GP, Joshua B, Kaplan MJ, Longaker MT, Weissman IL (2010) Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271. Nature 466(7302): 133–137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bollag G, Freeman S, Lyons JF, Post LE (2003) Raf pathway inhibitors in oncology. Curr Opin Investig Drugs 4(12):1436–1441

    PubMed  CAS  Google Scholar 

  • Bollag G, Tsai J, Zhang J, Zhang C, Ibrahim P, Nolop K, Hirth P (2012) Vemurafenib: the first drug approved for BRAF-mutant cancer. Nat Rev Drug Discov 11(11): 873–886

    Article  CAS  PubMed  Google Scholar 

  • Boni A, Cogdill AP, Dang P, Udayakumar D, Njauw CN, Sloss CM, Ferrone CR, Flaherty KT, Lawrence DP, Fisher DE, Tsao H, Wargo JA (2010) Selective BRAFV600E inhibition enhances T-cell recognition of melanoma without affecting lymphocyte function. Cancer Res 70(13):5213–5219

    Article  CAS  PubMed  Google Scholar 

  • Carvajal RD, Sosman JA, Quevedo JF, Milhem MM, Joshua AM, Kudchadkar RR, Linette GP, Gajewski TF, Lutzky J, Lawson DH, Lao CD, Flynn PJ, Albertini MR, Sato T, Lewis K, Doyle A, Ancell K, Panageas KS, Bluth M, Hedvat C, Erinjeri J, Ambrosini G, Marr B, Abramson DH, Dickson MA, Wolchok JD, Chapman PB, Schwartz GK (2014) Effect of selumetinib vs chemotherapy on progression-free survival in uveal melanoma: a randomized clinical trial. JAMA 311(23):2397–2405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caunt CJ, Sale MJ, Smith PD, Cook SJ (2015) MEK1 and MEK2 inhibitors and cancer therapy: the long and winding road. Nat Rev Cancer 15(10):577–592

    Article  CAS  PubMed  Google Scholar 

  • Cheng Y, Tian H (2017) Current development status of MEK inhibitors. Molecules 22(10): E1551

    Google Scholar 

  • Cooper ZA, Reuben A, Austin-Breneman J, Wargo JA (2015) Does it MEK a difference? Understanding immune effects of targeted therapy. Clin Cancer Res 21(14):3102–3104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cox AD, Der CJ (2012) The RAF inhibitor paradox revisited. Cancer Cell 21(2):147–149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cox AD, Der CJ, Philips MR (2015) Targeting RAS membrane association: back to the future for anti-RAS drug discovery? Clin Cancer Res 21(8):1819–1827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Das Thakur M, Salangsang F, Landman AS, Sellers WR, Pryer NK, Levesque MP, Dummer R, McMahon M, Stuart DD (2013) Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance. Nature 494(7436):251–255

    Article  CAS  PubMed  Google Scholar 

  • Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA (2002) Mutations of the BRAF gene in human cancer. Nature 417(6892):949–954

    Article  CAS  Google Scholar 

  • Drilon A, Siena S, Ou SI, Patel M, Ahn MJ, Lee J, Bauer TM, Farago AF, Wheler JJ, Liu SV, Doebele R, Giannetta L, Cerea G, Marrapese G, Schirru M, Amatu A, Bencardino K, Palmeri L, Sartore-Bianchi A, Vanzulli A, Cresta S, Damian S, Duca M, Ardini E, Li G, Christiansen J, Kowalski K, Johnson AD, Patel R, Luo D, Chow-Maneval E, Hornby Z, Multani PS, Shaw AT, De Braud FG (2017) Safety and antitumor activity of the multitargeted pan-TRK, ROS1, and ALK inhibitor Entrectinib: combined results from two phase I trials (ALKA-372-001 and STARTRK-1). Cancer Discov 7(4):400–409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dummer R, Schadendorf D, Ascierto PA, Arance A, Dutriaux C, Di Giacomo AM, Rutkowski P, Del Vecchio M, Gutzmer R, Mandala M, Thomas L, Demidov L, Garbe C, Hogg D, Liszkay G, Queirolo P, Wasserman E, Ford J, Weill M, Sirulnik LA, Jehl V, Bozon V, Long GV, Flaherty K (2017) Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 18(4):435–445

    Article  CAS  Google Scholar 

  • Flaherty K (2017) In the pipeline: encorafenib and binimetinib in BRAF-mutated melanoma. Clin Adv Hematol Oncol 15(10):745–747

    PubMed  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674

    Article  CAS  Google Scholar 

  • Heinzerling L, Kuhnapfel S, Meckbach D, Baiter M, Kaempgen E, Keikavoussi P, Schuler G, Agaimy A, Bauer J, Hartmann A, Kiesewetter F, Schneider-Stock R (2013) Rare BRAF mutations in melanoma patients: implications for molecular testing in clinical practice. Br J Cancer 108(10):2164–2171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Holderfield M, Deuker MM, McCormick F, McMahon M (2014) Targeting RAF kinases for cancer therapy: BRAF-mutated melanoma and beyond. Nat Rev Cancer 14(7):455–467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Izar B, Sharfman W, Hodi FS, Lawrence D, Flaherty KT, Amaravadi R, Kim KB, Puzanov I, Sosman J, Dummer R, Goldinger SM, Lam L, Kakar S, Tang Z, Krieter O, McDermott DF, Atkins MB (2017) A first-in-human phase I, multicenter, open-label, dose-escalation study of the oral RAF/VEGFR-2 inhibitor (RAF265) in locally advanced or metastatic melanoma independent from BRAF mutation status. Cancer Med 6(8):1904–1914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johnson DB, Menzies AM, Zimmer L, Eroglu Z, Ye F, Zhao S, Rizos H, Sucker A, Scolyer RA, Gutzmer R, Gogas H, Kefford RF, Thompson JF, Becker JC, Berking C, Egberts F, Loquai C, Goldinger SM, Pupo GM, Hugo W, Kong X, Garraway LA, Sosman JA, Ribas A, Lo RS, Long GV, Schadendorf D (2015) Acquired BRAF inhibitor resistance: a multicenter meta-analysis of the spectrum and frequencies, clinical behaviour, and phenotypic associations of resistance mechanisms. Eur J Cancer 51(18): 2792–2799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • King AJ, Arnone MR, Bleam MR, Moss KG, Yang J, Fedorowicz KE, Smitheman KN, Erhardt JA, Hughes-Earle A, Kane-Carson LS, Sinnamon RH, Qi H, Rheault TR, Uehling DE, Laquerre SG (2013) Dabrafenib; preclinical characterization, increased efficacy when combined with trametinib, while BRAF/MEK tool combination reduced skin lesions. PLoS One 8(7):e67583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Komatsubara KM, Manson DK, Carvajal RD (2016) Selumetinib for the treatment of metastatic uveal melanoma: past and future perspectives. Future Oncol 12(11):1331–1344

    Article  CAS  PubMed  Google Scholar 

  • Konieczkowski DJ, Johannessen CM, Abudayyeh O, Kim JW, Cooper ZA, Piris A, Frederick DT, Barzily-Rokni M, Straussman R, Haq R, Fisher DE, Mesirov JP, Hahn WC, Flaherty KT, Wargo JA, Tamayo P, Garraway LA (2014) A melanoma cell state distinction influences sensitivity to MAPK pathway inhibitors. Cancer Discov 4(7):816–827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kortum RL, Morrison DK (2015) Path forward for RAF therapies: inhibition of monomers and dimers. Cancer Cell 28(3):279–281

    Article  CAS  PubMed  Google Scholar 

  • Luke JJ, Flaherty KT, Ribas A, Long GV (2017) Targeted agents and immunotherapies: optimizing outcomes in melanoma. Nat Rev Clin Oncol 14(8):463–482

    Article  CAS  Google Scholar 

  • Maki RG, Blay JY, Demetri GD, Fletcher JA, Joensuu H, Martin-Broto J, Nishida T, Reichardt P, Schoffski P, Trent JC (2015) Key issues in the clinical management of gastrointestinal stromal tumors: an expert discussion. Oncologist 20(7):823–830

    Article  PubMed  PubMed Central  Google Scholar 

  • Neilsen BK, Frodyma DE, Lewis RE, Fisher KW (2017) KSR as a therapeutic target for Ras-dependent cancers. Expert Opin Ther Targets 21(5):499–509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nissan MH, Pratilas CA, Jones AM, Ramirez R, Won H, Liu C, Tiwari S, Kong L, Hanrahan AJ, Yao Z, Merghoub T, Ribas A, Chapman PB, Yaeger R, Taylor BS, Schultz N, Berger MF, Rosen N, Solit DB (2014) Loss of NF1 in cutaneous melanoma is associated with RAS activation and MEK dependence. Cancer Res 74(8):2340–2350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ohren JF, Chen H, Pavlovsky A, Whitehead C, Zhang E, Kuffa P, Yan C, McConnell P, Spessard C, Banotai C, Mueller WT, Delaney A, Omer C, Sebolt-Leopold J, Dudley DT, Leung IK, Flamme C, Warmus J, Kaufman M, Barrett S, Tecle H, Hasemann CA (2004) Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition. Nat Struct Mol Biol 11(12): 1192–1197

    Article  CAS  PubMed  Google Scholar 

  • Pelosof L, Lemery S, Casak S, Jiang X, Rodriguez L, Pierre V, Bi Y, Liu J, Zirkelbach JF, Patel A, Goldberg KB, McKee AE, Keegan P, Pazdur R (2018) Benefit-risk summary of regorafenib for the treatment of patients with advanced hepatocellular carcinoma that has progressed on sorafenib. Oncologist 23(4):496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Philpott C, Tovell H, Frayling IM, Cooper DN, Upadhyaya M (2017) The NF1 somatic mutational landscape in sporadic human cancers. Hum Genomics 11(1):13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pollock PM, Harper UL, Hansen KS, Yudt LM, Stark M, Robbins CM, Moses TY, Hostetter G, Wagner U, Kakareka J, Salem G, Pohida T, Heenan P, Duray P, Kallioniemi O, Hayward NK, Trent JM, Meltzer PS (2003) High frequency of BRAF mutations in nevi. Nat Genet 33(1):19–20

    Article  CAS  PubMed  Google Scholar 

  • Postow MA, Carvajal RD (2012) Therapeutic implications of KIT in melanoma. Cancer J 18(2):137–141

    Article  CAS  PubMed  Google Scholar 

  • Pratilas CA, Solit DB (2010) Targeting the mitogen-activated protein kinase pathway: physiological feedback and drug response. Clin Cancer Res 16(13): 3329–3334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rajakulendran T, Sahmi M, Lefrancois M, Sicheri F, Therrien M (2009) A dimerization-dependent mechanism drives RAF catalytic activation. Nature 461(7263):542–545

    Article  CAS  PubMed  Google Scholar 

  • Samatar AA, Poulikakos PI (2014) Targeting RAS-ERK signalling in cancer: promises and challenges. Nat Rev Drug Discov 13(12):928–942

    Article  CAS  PubMed  Google Scholar 

  • Sebolt-Leopold JS, Herrera R (2004) Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer 4(12):937–947

    Article  CAS  PubMed  Google Scholar 

  • Sharma SV, Lee DY, Li B, Quinlan MP, Takahashi F, Maheswaran S, McDermott U, Azizian N, Zou L, Fischbach MA, Wong KK, Brandstetter K, Wittner B, Ramaswamy S, Classon M, Settleman J (2010) A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell 141(1):69–80

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi H, Hugo W, Kong X, Hong A, Koya RC, Moriceau G, Chodon T, Guo R, Johnson DB, Dahlman KB, Kelley MC, Kefford RF, Chmielowski B, Glaspy JA, Sosman JA, van Baren N, Long GV, Ribas A, Lo RS (2014) Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy. Cancer Discov 4(1):80–93

    Article  CAS  Google Scholar 

  • Simanshu DK, Nissley DV, McCormick F (2017) RAS proteins and their regulators in human disease. Cell 170(1):17–33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Solit DB, Rosen N (2011) Resistance to BRAF inhibition in melanomas. N Engl J Med 364(8):772–774

    Article  CAS  PubMed  Google Scholar 

  • Solit DB, Rosen N (2014) Towards a unified model of RAF inhibitor resistance. Cancer Discov 4(1):27–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Straussman R, Morikawa T, Shee K, Barzily-Rokni M, Qian ZR, Du J, Davis A, Mongare MM, Gould J, Frederick DT, Cooper ZA, Chapman PB, Solit DB, Ribas A, Lo RS, Flaherty KT, Ogino S, Wargo JA, Golub TR (2012) Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature 487(7408):500–504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, Reis-Filho JS, Kong X, Koya RC, Flaherty KT, Chapman PB, Kim MJ, Hayward R, Martin M, Yang H, Wang Q, Hilton H, Hang JS, Noe J, Lambros M, Geyer F, Dhomen N, Niculescu-Duvaz I, Zambon A, Niculescu-Duvaz D, Preece N, Robert L, Otte NJ, Mok S, Kee D, Ma Y, Zhang C, Habets G, Burton EA, Wong B, Nguyen H, Kockx M, Andries L, Lestini B, Nolop KB, Lee RJ, Joe AK, Troy JL, Gonzalez R, Hutson TE, Puzanov I, Chmielowski B, Springer CJ, McArthur GA, Sosman JA, Lo RS, Ribas A, Marais R (2012) RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med 366(3):207–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sullivan RJ, Infante JR, Janku F, Wong DJL, Sosman JA, Keedy V, Patel MR, Shapiro GI, Mier JW, Tolcher AW, Wang-Gillam A, Sznol M, Flaherty K, Buchbinder E, Carvajal RD, Varghese AM, Lacouture ME, Ribas A, Patel SP, DeCrescenzo GA, Emery CM, Groover AL, Saha S, Varterasian M, Welsch DJ, Hyman DM, Li BT (2018) First-in-class ERK1/2 inhibitor Ulixertinib (BVD-523) in patients with MAPK mutant advanced solid tumors: results of a phase I dose-escalation and expansion study. Cancer Discov 8(2):184–195

    Article  CAS  PubMed  Google Scholar 

  • Vigil D, Cherfils J, Rossman KL, Der CJ (2010) Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy? Nat Rev Cancer 10(12): 842–857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wan PT, Garnett MJ, Roe SM, Lee S, Niculescu-Duvaz D, Good VM, Jones CM, Marshall CJ, Springer CJ, Barford D, Marais R (2004) Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 116(6):855–867

    Article  CAS  PubMed  Google Scholar 

  • Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, Smith RA, Schwartz B, Simantov R, Kelley S (2006) Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov 5(10):835–844

    Article  CAS  PubMed  Google Scholar 

  • Wilson TR, Fridlyand J, Yan Y, Penuel E, Burton L, Chan E, Peng J, Lin E, Wang Y, Sosman J, Ribas A, Li J, Moffat J, Sutherlin DP, Koeppen H, Merchant M, Neve R, Settleman J (2012) Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors. Nature 487(7408):505–509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yao Z, Torres NM, Tao A, Gao Y, Luo L, Li Q, de Stanchina E, Abdel-Wahab O, Solit DB, Poulikakos PI, Rosen N (2015) BRAF mutants evade ERK-dependent feedback by different mechanisms that determine their sensitivity to pharmacologic inhibition. Cancer Cell 28(3):370–383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yao Z, Yaeger R, Rodrik-Outmezguine VS, Tao A, Torres NM, Chang MT, Drosten M, Zhao H, Cecchi F, Hembrough T, Michels J, Baumert H, Miles L, Campbell NM, de Stanchina E, Solit DB, Barbacid M, Taylor BS, Rosen N (2017) Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS. Nature 548(7666):234–238

    PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang C, Spevak W, Zhang Y, Burton EA, Ma Y, Habets G, Zhang J, Lin J, Ewing T, Matusow B, Tsang G, Marimuthu A, Cho H, Wu G, Wang W, Fong D, Nguyen H, Shi S, Womack P, Nespi M, Shellooe R, Carias H, Powell B, Light E, Sanftner L, Walters J, Tsai J, West BL, Visor G, Rezaei H, Lin PS, Nolop K, Ibrahim PN, Hirth P, Bollag G (2015) RAF inhibitors that evade paradoxical MAPK pathway activation. Nature 526(7574):583–586

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Plexxikon Inc., Berkeley, CA, USA

    Gideon Bollag

  2. Henri and Belinda Termeer Center for Targeted Therapies, MGH Cancer Center, Cambridge, MA, USA

    Keith T. Flaherty

Authors
  1. Gideon Bollag
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Keith T. Flaherty
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gideon Bollag .

Editor information

Editors and Affiliations

  1. Harvard/MGH Cutaneous Biology Research C Massachusetts General Hospital, Boston, Massachusetts, USA

    David E. Fisher

  2. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

    Boris C. Bastian

Section Editor information

  1. Department of Dermatology, Harvard/MGH Cutaneous Biology Research Center, and Melanoma Program, MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    David E. Fisher

  2. QIMR Berghofer Medical Research Institute, Herston, QLD, Australia

    Nick Hayward

  3. QIMR Berghofer Medical Research Institute, Herston, QLD, Australia

    David C. Whiteman

  4. Henri and Belinda Termeer Center for Targeted Therapies, MGH Cancer Center, Boston, MA, USA

    Keith T. Flaherty

  5. Framingham, MA, USA

    F. Stephen Hodi

  6. Department of Medicine, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA, USA

    F. Stephen Hodi

  7. Auburndale, MA, USA

    Hensin Tsao

  8. Harvard-MIT Health Sciences and Technology, Cambridge, MA, USA

    Hensin Tsao

  9. Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    Glenn Merlino

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media, LLC, part of Springer Nature

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Bollag, G., Flaherty, K.T. (2018). Principles of Targeted Therapy. In: Fisher, D., Bastian, B. (eds) Melanoma. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7322-0_35-1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-7322-0_35-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-7322-0

  • Online ISBN: 978-1-4614-7322-0

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation