Melanoma brain metastasis: overview of current management and emerging targeted therapies.
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.
Brain Tumor Center and Neuro-Oncology Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Ekokobe
E
Fonkem
Erik J
EJ
Uhlmann
Scott R
SR
Floyd
Anand
A
Mahadevan
Ekkehard
E
Kasper
Omar
O
Eton
Eric T
ET
Wong
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000737:chemistry; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary* / Q000628:therapy; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D003131:Combined Modality Therapy; D019317:Evidence-Based Medicine; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007211:Indoles / Q000627:therapeutic use; D000074324:Ipilimumab; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary* / Q000628:therapy; D058990:Molecular Targeted Therapy / Q000639:trends; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000627:therapeutic use; D000077484:Vemurafenib
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007211:Indoles; D000074324:Ipilimumab; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf