title: Recent Progress in Mutation-driven Therapy, Immunotherapy and Combination Therapy for the Treatment of Melanoma.
abstract: With increases in our understanding of the human genome and immune system, the treatment armamentarium for melanoma has benefitted from the development and approval of BRAF inhibitors, MEK inhibitors, immune checkpoint modulators via cytotoxic T-lymphocyte antigen-4 blockade, and PD-1 and PD-L1 inhibitors. These advances, however, have raised questions about combination therapy, the optimal sequential use of these agents, the limited assessment of response using traditional metrics, and the optimal selection of the population to be treated. In this review we summarize recent breakthroughs and then itemize the development of newer agents, potential prognostic and predictive biomarkers, resistance mechanisms, and strategies of combination therapy. We also emphasize the multifaceted attributes of immunotherapy in terms of durable responses and longterm survival that paradoxically necessitate further research into the underlying mechanisms and longer patient follow-up.
authors.affiliation: Department of Internal Medicine, Naef K. Bassile Cancer Institute, American University of Beirut Medical Center. P.O. Box: 11-0236, Riad El Solh 1107 2020, Beirut - Lebanon. Select country.
authors.forename: Hazem I
authors.initials: HI
authors.lastname: Assi
authors.forename: Rita E
authors.initials: RE
authors.lastname: Assi
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D060908:CTLA-4 Antigen / Q000276:immunology; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods*; D007211:Indoles / Q000627:therapeutic use; D008545:Melanoma / Q000235:genetics / Q000628:therapy*; D009154:Mutation; D010091:Oximes / Q000627:therapeutic use; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D011728:Pyridones / Q000627:therapeutic use; D011744:Pyrimidinones / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007093:Imidazoles; D007211:Indoles; D010091:Oximes; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011728:Pyridones; D011744:Pyrimidinones; D013449:Sulfonamides; D000077484:Vemurafenib; C560077:trametinib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib
keywords: BRAF inhibitors; CTLA-4 inhibitors; MEK inhibitors; Melanoma; PD-1 inhibitors; PD-L1 inhibitors; immunotherapy; mutationdriven
  therapy