Oncotarget

Reviews:

Management of intracranial melanomas in the era of precision medicine

Grace J. Young, Wenya Linda Bi, Winona W. Wu, Tanner M. Johanns, Gavin P. Dunn and Ian F. Dunn _

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Oncotarget. 2017; 8:89326-89347. https://doi.org/10.18632/oncotarget.19223

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Abstract

Grace J. Young1,*, Wenya Linda Bi1,2,*, Winona W. Wu1, Tanner M. Johanns3,4, Gavin P. Dunn4,5 and Ian F. Dunn1

1Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

2Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

3Division of Medical Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA

4Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA

5Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, USA

*These authors contributed equally to this work

Correspondence to:

Ian F. Dunn, email: idunn@partners.org

Gavin P. Dunn, email: gpdunn@wustl.edu

Keywords: intracranial melanoma, BRAF inhibition, targeted therapy, immunotherapy, anti-PD1

Received: October 04, 2016     Accepted: April 24, 2017     Published: July 13, 2017

ABSTRACT

Melanoma is the most lethal of skin cancers, in part because of its proclivity for rapid and distant metastasis. It is also potentially the most neurotropic cancer in terms of probability of CNS metastasis from the primary lesion. Despite surgical resection and radiotherapy, prognosis remains guarded for patients with brain metastases. Over the past five years, a new domain of personalized therapy has emerged for advanced melanoma patients with the introduction of BRAF and other MAP kinase pathway inhibitors, immunotherapy, and combinatory therapeutic strategies. By targeting critical cellular signaling pathways and unleashing the adaptive immune response against tumor antigens, a subset of melanoma patients have demonstrated remarkable responses to these treatments. Over time, acquired resistance to these modalities inexorably develops, providing new challenges to overcome. We review the rapidly evolving terrain for intracranial melanoma treatment, address likely and potential mechanisms of resistance, as well as evaluate promising future therapeutic approaches currently under clinical investigation.


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