Targeting the PD-1 pathway: A promising future for the treatment of melanoma

Andrew Mamalis, Manveer Garcha, Jared Jagdeo

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Advanced melanoma presents a significant therapeutic challenge to clinicians. Many therapies for metastatic melanoma are limited by low response rates, severe toxicities, and/or relatively short response duration. Cancer immunotherapies that act as immune-checkpoint inhibitors to block the localized immune suppression mechanisms utilized by tumors are undergoing development and clinical trials. A clinically relevant immune escape mechanism in melanoma is the activation of the programmed cell death-1 (PD-1) receptor on infiltrating T cells. Activating PD-1 triggers an immune checkpoint resulting in inhibition of T cells directed against melanoma antigens and prevents the immune system from combating the melanoma. In Phase I clinical trials, two anti-PD1 therapies, Nivolumab and MK-3475, that block the PD-1 receptor to enable T cell killing have demonstrated objective tumor responses in patients with advanced melanoma. The purpose of this review is to present the available clinical evidence on anti-PD-1 and anti-PD-L1 immunotherapy for the treatment of advanced melanoma. We also discuss limitations associated with anti-PD-1 therapy. The blockade of the PD-1-PD-L1 pathway has shown promising results in clinical trials and has revolutionized melanoma immunotherapy.

Original languageEnglish (US)
Pages (from-to)511-519
Number of pages9
JournalArchives of Dermatological Research
Volume306
Issue number6
DOIs
StatePublished - 2014

Keywords

  • BRAF
  • Immunotherapy
  • Ipilimumab
  • Melanoma
  • MK-3475
  • Nivolumab
  • PD-1
  • PD-L1
  • Programmed cell death receptor 1

ASJC Scopus subject areas

  • Dermatology

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