Re-Thinking Therapeutic Development for CNS Metastatic Disease

Authors

Chantal Saberian
Michael A Davies

Publication Date

1-1-2022

Journal

Experimental Dermatology

Abstract

There has been unprecedented progress in the development of systemic therapies for patients with metastatic melanoma over the last decade. There is now tremendous potential and momentum to further and markedly reduce the impact of this disease. However, developing more effective treatments for metastases to the CNS remains a critical challenge for patients with melanoma. Melanoma patients with active CNS metastases have largely been excluded from both early-phase and registration trials for all currently approved targeted and immune therapies for this disease. While this exclusion has generally been justified in clinical research due to concerns about poor prognosis, lack of CNS penetration of agents and/or risk of toxicities, recent post-approval trials have shown the feasibility, safety and clinical benefit of clinical investigation in these patients. These trials have also identified key areas for which more effective strategies are needed. In parallel, recent translational and preclinical research has provided insights into novel immune, molecular and metabolic features of melanoma brain metastases that may mediate the aggressive biology and therapeutic resistance of these tumors. Together, these advances suggest the need for new paradigms for therapeutic development for melanoma patients with CNS metastasis.

Keywords

Brain Neoplasms, Clinical Trials as Topic, Humans, Immunotherapy, Melanoma, Molecular Targeted Therapy, Skin Neoplasms, brain metastasis, cancer, immunotherapy, melanoma, targeted therapy

DOI

10.1111/exd.14413

PMID

34152638

PMCID

PMC11373440

PubMedCentral® Posted Date

9-4-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes