Advances in Targeted Therapy for Melanoma

Abstract: Metastatic melanoma remains an aggressive malignancy conferring a very poor prognosis, and standard chemotherapeutic and immunologic treatments have not demonstrated an overall survival benefit. No molecularly targeted therapy is approved for the treatment of advanced melanoma. Melanoma is a molecularly heterogeneous malignancy, and optimal treatment in a given patient is likely to depend on the presence of specific molecular abnormalities. Aberrations in components of signal transduction pathways have been identified that modulate melanoma proliferation and survival. Mutations that activate the mitogen activated protein kinase (MAPK) pathway via BRAF or NRAS are present in the majority of melanomas arising on skin intermittently exposed to the sun. Mutations that activate the KIT oncogene are more commonly present in melanomas arising from mucosal, acral, or chronic sun-damaged sites. Inhibitors of the MAPK pathway and of KIT are currently undergoing clinical investigation. In this article, we review advances in targeted strategies to treat different subgroups of patients with melanoma.

BRAF Testing in Advanced Colorectal Cancer: Is It Ready for Prime Time?

Abstract: iven that KRAS mutant colorectal tumors do not respond to anti-EGFR monoclonal antibodies such as cetuximab or panitumumab, it is now standard that all patients with metastatic colorectal cancer who are candidates for these therapies undergo KRAS testing. BRAF encodes a protein kinase, which is involved in intracellular signaling and cell growth and is a principal downstream effector of KRAS. BRAF is now increasingly being investigated in metastatic colorectal carcinoma. BRAF mutations occur in less than 10–15% of tumors and appear to be poor prognostic markers. However the predictive nature of this biomarker is yet undefined. This article will review the evidence behind both KRAS and BRAF testing in metastatic colorectal cancer.