Melanoma: Advances in Targeted Therapy and Molecular Markers

被引:14
作者
DePeralta, Danielle K. [1 ]
Boland, Genevieve M. [1 ]
机构
[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA 02163 USA
关键词
METASTATIC MELANOMA; OPEN-LABEL; CUTANEOUS MELANOMA; IMPROVED SURVIVAL; COMPLETE RESPONSE; MUCOSAL MELANOMA; MEK INHIBITION; BRAF MUTATIONS; PHASE-II; NRAS;
D O I
10.1245/s10434-015-4702-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In recent years, there have been dramatic improvements in the diagnosis and treatment of patients with melanoma. The development of molecular markers and associated targeted therapies have given new hope to subsets of patients with advanced disease. Here we discuss the most important advances in molecular targeted therapy and how these developments are likely to affect the practice of the clinical surgeon. Germ-line and somatic mutations are common in melanoma and provide prognostic information that can now be harnessed to provide a more personalized approach to cancer treatment. BRAF mutation at the V600 position is the most commonly identified mutation in patients with melanoma. Treatment with targeted inhibitors in patients with BRAF-mutant melanoma has afforded dramatic responses in about half of selected patients. Unfortunately, disease control is not durable and recurrences are common. We predict an increasing role for the surgeon in the multidisciplinary treatment of patients with metastatic disease, as well as a role for molecular profiling in patients with high-risk early stage disease. Further, we are only beginning to understand the prognostic significance of various gene mutations in patients with melanoma.
引用
收藏
页码:3451 / 3458
页数:8
相关论文
共 69 条
[11]   Mutations of the BRAF gene in human cancer [J].
Davies, H ;
Bignell, GR ;
Cox, C ;
Stephens, P ;
Edkins, S ;
Clegg, S ;
Teague, J ;
Woffendin, H ;
Garnett, MJ ;
Bottomley, W ;
Davis, N ;
Dicks, N ;
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, JWC ;
Leung, SY ;
Yuen, ST ;
Weber, BL ;
Siegler, HF ;
Darrow, TL ;
Paterson, H ;
Marais, R ;
Marshall, CJ ;
Wooster, R .
NATURE, 2002, 417 (6892) :949-954
[12]   Clinical outcome and pathological features associated with NRAS mutation in cutaneous melanoma [J].
Devitt, Bianca ;
Liu, Wendy ;
Salemi, Renato ;
Wolfe, Rory ;
Kelly, John ;
Tzen, Chin-Yuan ;
Dobrovic, Alexander ;
McArthur, Grant .
PIGMENT CELL & MELANOMA RESEARCH, 2011, 24 (04) :666-672
[13]   Phase II Study of Temozolomide (TMZ) and Everolimus (RAD001) Therapy for Metastatic Melanoma A North Central Cancer Treatment Group Study, N0675 [J].
Dronca, Roxana S. ;
Allred, Jacob B. ;
Perez, Domingo G. ;
Nevala, Wendy K. ;
Lieser, Elizabeth A. T. ;
Thompson, Michael ;
Maples, William J. ;
Creagan, Edward T. ;
Pockaj, Barbara A. ;
Kaur, Judith S. ;
Moore, Timothy D. ;
Marchello, Benjamin T. ;
Markovic, Svetomir N. .
AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS, 2014, 37 (04) :369-376
[14]  
Essner R, 1998, CANCER, V82, P309, DOI 10.1002/(SICI)1097-0142(19980115)82:2<317::AID-CNCR10>3.0.CO
[15]  
2-1
[16]   Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial [J].
Falchook, Gerald S. ;
Long, Georgina V. ;
Kurzrock, Razelle ;
Kim, Kevin B. ;
Arkenau, Tobias H. ;
Brown, Michael P. ;
Hamid, Omid ;
Infante, Jeffrey R. ;
Millward, Michael ;
Pavlick, Anna C. ;
O'Day, Steven J. ;
Blackman, Samuel C. ;
Curtis, C. Martin ;
Lebowitz, Peter ;
Ma, Bo ;
Ouellet, Daniele ;
Kefford, Richard F. .
LANCET, 2012, 379 (9829) :1893-1901
[17]   Acquired and intrinsic BRAF inhibitor resistance in BRAF V600E mutant melanoma [J].
Fedorenko, Inna V. ;
Paraiso, Kim H. T. ;
Smalley, Keiran S. M. .
BIOCHEMICAL PHARMACOLOGY, 2011, 82 (03) :201-209
[18]   Improved Survival with MEK Inhibition in BRAF-Mutated Melanoma [J].
Flaherty, Keith T. ;
Robert, Caroline ;
Hersey, Peter ;
Nathan, Paul ;
Garbe, Claus ;
Milhem, Mohammed ;
Demidov, Lev V. ;
Hassel, Jessica C. ;
Rutkowski, Piotr ;
Mohr, Peter ;
Dummer, Reinhard ;
Trefzer, Uwe ;
Larkin, James M. G. ;
Utikal, Jochen ;
Dreno, Brigitte ;
Nyakas, Marta ;
Middleton, Mark R. ;
Becker, Juergen C. ;
Casey, Michelle ;
Sherman, Laurie J. ;
Wu, Frank S. ;
Ouellet, Daniele ;
Martin, Anne-Marie ;
Patel, Kiran ;
Schadendorf, Dirk .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 367 (02) :107-114
[19]   Clinical Applications of Melanoma Genetics [J].
Gabree, Michele ;
Patel, Devanshi ;
Rodgers, Linda .
CURRENT TREATMENT OPTIONS IN ONCOLOGY, 2014, 15 (02) :336-350
[20]   Examination of mutations in BRAF, NRAS, and PTEN in primary cutaneous melanoma [J].
Goel, Vikas K. ;
Lazar, Alexander J. F. ;
Warneke, Carla L. ;
Redston, Mark S. ;
Haluska, Frank G. .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2006, 126 (01) :154-160