title: Metastatic Melanoma: Insights Into the Evolution of the Treatments and Future Challenges.
abstract: Melanoma is the deadliest form of skin cancer. While associated survival prognosis is good when diagnosed early, it dramatically drops when melanoma progresses into its metastatic form. Prior to 2011, the favored therapies include interleukin-2 and chemotherapies, regardless of their low efficiency and their toxicity. Following key biological findings, two new types of therapy have been approved. First, there are the targeted therapies, which rely on small molecule B-Raf and MEK inhibitors and allow the treatment of patients with B-Raf mutated melanoma. Second, there are the immunotherapies, with anti-CTLA-4 and anti-PD-1 antibodies that are used for patients harboring a B-Raf wild-type status. Both approaches have significantly improved patient survival, compared with alkylating agents, in the treatment of unresectable melanoma. Herein, we review the evolution of the treatment of melanoma starting from early discoveries to current therapies. A focus will be provided on drug discovery, synthesis, and mode of action of relevant drugs and the future directions of the domain to overcome the emergence of the resistance events.
authors: Institut de Chimie de Nice UMR UNS-CNRS 7272, Nice, France.
authors: Antoine
authors: A
authors: Millet
authors: Institut de Chimie de Nice UMR UNS-CNRS 7272, Nice, France.
authors: Anthony R
authors: AR
authors: Martin
authors: Institut de Chimie de Nice UMR UNS-CNRS 7272, Nice, France.
authors: Cyril
authors: C
authors: Ronco
authors: INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Equipe Biologie et Pathologie des cellules mélanocytaires: de la pigmentation cutanée au mélanome, Nice, France.|Université de Nice Sophia Antipolis, UFR de Médecine, Nice, France.|Service de Dermatologie, Hôpital Archet II, CHU Nice, France.
authors: Stéphane
authors: S
authors: Rocchi
authors: Institut de Chimie de Nice UMR UNS-CNRS 7272, Nice, France.
authors: Rachid
authors: R
authors: Benhida
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology / Q000628:therapy*; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; D047428:Protein Kinase Inhibitors
keywords: B-Raf/MEK inhibitors; drug resistance; immunotherapies; melanoma; targeted therapies