Melanoma brain metastasis: overview of current management and emerging targeted therapies

Ekokobe Fonkem Brain Tumor Center and Neuro-Oncology Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Neurosurgery, Scott and White Hospital, Texas A&M College of Medicine, Temple, TX, USA; Brain Tumor Center and Neuro-Oncology Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Neurosurgery, Scott and White Hospital, Texas A&M College of Medicine, Temple, TX, USA

Erik J Uhlmann Brain Tumor Center and Neuro-Oncology Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Brain Tumor Center and Neuro-Oncology Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

Scott R Floyd Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

Anand Mahadevan Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

Ekkehard Kasper Department of Surgery (Division of Neurosurgery), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Surgery (Division of Neurosurgery), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

Omar Eton Department of Medicine (Division of Hematology/Oncology), Boston Medical Center, Boston University School of Medicine, Boston, MA, USA; Department of Medicine (Division of Hematology/Oncology), Boston Medical Center, Boston University School of Medicine, Boston, MA, USA

Eric T Wong Brain Tumor Center and Neuro-Oncology Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Brain Tumor Center and Neuro-Oncology Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. [email protected]

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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.

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Acknowledgements

The authors thank Nkengafeh Asong and Edwin Lok for their assistance with this review.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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Melanoma brain metastasis: overview of current management and emerging targeted therapies

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Melanoma brain metastasis: overview of current management and emerging targeted therapies

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