Molecular insights into melanoma brain metastases

Cancer. 2017 Jun 1;123(S11):2163-2175. doi: 10.1002/cncr.30594.

Abstract

Substantial proportions of patients with metastatic melanoma develop brain metastases during the course of their disease, often resulting in significant morbidity and death. Despite recent advances with BRAF/MEK and immune-checkpoint inhibitors in the treatment of patients who have melanoma with extracerebral metastases, patients who have melanoma brain metastases still have poor overall survival, highlighting the need for further therapy options. A deeper understanding of the molecular pathways involved in the development of melanoma brain metastases is required to develop more brain-specific therapies. Here, the authors summarize the currently known preclinical data and describe steps involved in the development of melanoma brain metastases. Only by knowing the molecular background is it possible to design new therapeutic agents that can be used to improve the outcome of patients with melanoma brain metastases. Cancer 2017;123:2163-75. © 2017 American Cancer Society.

Keywords: blood-brain barrier; brain metastasis; brain parenchyma; immune cells; immunotherapies; melanoma; targeted therapies.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • B7-H1 Antigen
  • Blood-Brain Barrier
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / secondary
  • Brain Neoplasms / therapy
  • Cell Adhesion
  • Cranial Irradiation
  • Cytokines / metabolism
  • Extracellular Matrix / metabolism
  • Fibroblast Growth Factor 2 / metabolism
  • Glucuronidase / metabolism
  • Humans
  • Immunotherapy
  • Integrins / metabolism
  • Matrix Metalloproteinase 2 / metabolism
  • Melanoma / metabolism*
  • Melanoma / secondary
  • Melanoma / therapy
  • Molecular Targeted Therapy
  • Neovascularization, Pathologic / metabolism
  • Radiosurgery
  • Receptors, CCR4 / metabolism
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Transforming Growth Factor beta2 / metabolism
  • Tumor Escape
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antineoplastic Agents
  • B7-H1 Antigen
  • Cytokines
  • Integrins
  • Receptors, CCR4
  • Transforming Growth Factor beta2
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • heparanase
  • Glucuronidase
  • Matrix Metalloproteinase 2