Targeting Oncogenic Drivers and the Immune System in Melanoma
AuthorMcArthur, Grant A.; Ribas, Antoni
Source TitleJOURNAL OF CLINICAL ONCOLOGY
PublisherAMER SOC CLINICAL ONCOLOGY
University of Melbourne Author/sMcArthur, Grant
AffiliationSir Peter MacCallum Department of Oncology
Document TypeJournal Article
Access StatusThis item is currently not available from this repository
NHMRC Grant codeNHMRC/1002655
Fulltext embargoed for: 12 months post date of publication
Melanoma is one of the most common cancers in Western countries but has defied the trend of reductions in age-adjusted mortality observed in most other cancers in recent years. Biologically, melanoma is characterized by a high propensity to metastasize at low tumor volumes necessitating the need for effective drug therapies to support efforts in prevention and early detection for reducing mortality. Efforts to study the clinical biology of melanoma have led to a new understanding of the disease, with genomic studies identifying several targetable oncogenes, in particular the protein kinases BRAF and KIT. Biologic studies have also identified a variety of immunologic targets, including the programmed death 1 (PD-1) and cytotoxic T-cell lymphocyte-associated antigen 4 (CTLA-4) inhibitory molecules expressed on T lymphocytes. After several decades of clinical trials that failed to demonstrate improvement in overall survival in patients with advanced melanoma, small molecule inhibitors of BRAF or MEK and inhibition of CTLA-4 can improve survival in patients with advanced disease. These early clinical studies have provided a great opportunity to improve mortality in melanoma with the significant potential of combinations of signaling inhibitors or signaling inhibitors combined with immunologic agents, particularly when used in the adjuvant setting, and to transform the care of patients with this most challenging of cancers. J Clin Oncol 31:499-506.
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