Faculty Collaboration Database

Melanoma brain metastasis: overview of current management and emerging targeted therapies. Expert Rev Neurother 2012 Oct;12(10):1207-15

Date

10/23/2012

Pubmed ID

23082737

DOI

10.1586/ern.12.111

Scopus ID

2-s2.0-84867772278 (requires institutional sign-in at Scopus site)   64 Citations

Abstract

The high rate of brain metastasis in patients with advanced melanoma has been a clinical challenge for oncologists. Despite considerable progress made in the management of advanced melanoma over the past two decades, improvement in overall survival has been elusive. This is due to the high incidence of CNS metastases, which progress relentlessly and which are only anecdotally responsive to systemic therapies. Surgery, stereotactic radiosurgery and whole-brain radiotherapy with or without cytotoxic chemotherapy remain the mainstay of treatment. However, new drugs have been developed based on our improved understanding of the molecular signaling mechanisms responsible for host immune tolerance and for melanoma growth. In 2011, the US FDA approved two agents, one antagonizing each of these processes, for the treatment of advanced melanoma. The first is ipilimumab, an anti-CTLA-4 monoclonal antibody that enhances cellular immunity and reduces tolerance to tumor-associated antigens. The second is vemurafenib, an inhibitor that blocks the abnormal signaling for melanoma cellular growth in tumors that carry the BRAF(V600E) mutation. Both drugs have anecdotal clinical activity for brain metastasis and are being evaluated in clinical trial settings. Additional clinical trials of newer agents involving these pathways are also showing promise. Therefore, targeted therapies must be incorporated into the multimodality management of melanoma brain metastasis.

Author List

Fonkem E, Uhlmann EJ, Floyd SR, Mahadevan A, Kasper E, Eton O, Wong ET

Author

Ekokobe Fonkem DO Chair, Professor in the Neurology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antibodies, Monoclonal
Antigens, Neoplasm
Antineoplastic Agents
Brain Neoplasms
CTLA-4 Antigen
Combined Modality Therapy
Evidence-Based Medicine
Humans
Immunity, Cellular
Indoles
Ipilimumab
Melanoma
Molecular Targeted Therapy
Mutation
Proto-Oncogene Proteins B-raf
Signal Transduction
Sulfonamides