The biology and therapeutic management of melanoma brain metastases

Biochem Pharmacol. 2018 Jul:153:35-45. doi: 10.1016/j.bcp.2017.12.019. Epub 2017 Dec 24.

Abstract

The recent years have seen significant progress in the development of systemic therapies to treat patients with advanced melanoma. Use of these new treatment modalities, which include immune checkpoint inhibitors and small molecule BRAF inhibitors, lead to increased overall survival and better outcomes. Although revolutionary, these therapies are often less effective against melanoma brain metastases, and frequently the CNS is the major site of treatment failure. The development of brain metastases remains a serious complication of advanced melanoma that is associated with significant morbidity and mortality. New approaches to both prevent the development of brain metastases and treat established disease are urgently needed. In this review we will outline the mechanisms underlying the development of melanoma brain metastases and will discuss how new insights into metastasis biology are driving the development of new therapeutic strategies. Finally, we will describe the latest data from the ongoing clinical trials for patients with melanoma brain metastases.

Keywords: BRAF; Brain; Immunotherapy; Melanoma; Metastasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • Brain Neoplasms / immunology
  • Brain Neoplasms / secondary*
  • Brain Neoplasms / therapy*
  • Clinical Trials as Topic / methods
  • Disease Management*
  • Humans
  • Immunotherapy / methods
  • Immunotherapy / trends
  • Melanoma / immunology
  • Melanoma / therapy*
  • Molecular Targeted Therapy / methods
  • Molecular Targeted Therapy / trends
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Protein Kinase Inhibitors