title: PD-1 and PD-L1 inhibitors in melanoma treatment: past success, present application and future challenges.
abstract: Anti-programmed death (PD)-1 antibodies have now become the standard of care for advanced melanoma, with two drugs gaining US FDA approval in recent years: nivolumab and pembrolizumab. Both have demonstrated significant activity and durable response with a manageable toxicity profile. Despite initial success, ongoing challenges include patient selection and predictors of response, innate resistance and optimizing combination strategies. In this overview, we take a closer look at the history and development of therapeutic targets to the PD-1/PD-ligand (L)1 pathway, clinical evidence, availability of biomarkers and their limitations in clinical practice and future strategies to improve treatment outcomes.
authors.affiliation: Crown Princess Mary Cancer Centre, Westmead hospital, Westmead, NSW 2145, Australia.|Departments of Clinical Medicine and Biomedical Sciences, Macquarie University, NSW 2109, Australia.|Melanoma Institute Australia, North Sydney, NSW, Australia.
authors.forename: Jenny
authors.initials: J
authors.lastname: Lee
authors.affiliation: Crown Princess Mary Cancer Centre, Westmead hospital, Westmead, NSW 2145, Australia.|Departments of Clinical Medicine and Biomedical Sciences, Macquarie University, NSW 2109, Australia.|Melanoma Institute Australia, North Sydney, NSW, Australia.|University of Sydney, Sydney, NSW, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Kefford
authors.affiliation: Crown Princess Mary Cancer Centre, Westmead hospital, Westmead, NSW 2145, Australia.|Departments of Clinical Medicine and Biomedical Sciences, Macquarie University, NSW 2109, Australia.|Melanoma Institute Australia, North Sydney, NSW, Australia.|University of Sydney, Sydney, NSW, Australia.
authors.forename: Matteo
authors.initials: M
authors.lastname: Carlino
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D017277:Drug Approval; D006801:Humans; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D000077594:Nivolumab; D018579:Patient Selection; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology*; D014481:United States
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D054316:Biomarkers, Pharmacological; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab; C582435:pembrolizumab
keywords: biomarkers; immunotherapy; ipilimumab; melanoma; nivolumab; pembrolizumab; programmed death ligand-1; programmed death-1; tumor-infiltrating lymphocytes