Oncogene-Directed Small Molecule Inhibitors for the Treatment of Cutaneous Melanoma

Abstract

Achievements in cancer genetics and molecular biology have revolutionized the treatment options available for advanced melanoma. Patients with certain molecularly defined melanomas have been the most fortunate beneficiaries of recently US FDA-approved therapies that target aberrant MAPK pathway signaling, yet response rates and duration of response remain suboptimal. Furthermore, many patients harbor melanomas for which no approved targeted therapies currently exist. Since the approval of vemurafenib, a selective BRAF V600E inhibitor, in 2011, there has been a surge of preclinical and clinical studies aimed at developing novel targeted therapies for a wide range of molecularly defined melanomas. In this review, we will examine the present status and future potential of molecularly targeted therapies directed at the most significant oncogenic signaling pathways in melanoma.

The Double-Edged Proteins in Cancer Proteomes and the Generation of Induced Tumor-Suppressing Cells (iTSCs)

“…In about 90% of PDAC cases, K-Ras is mutated and the mutated K-Ras drives tumorigenic signaling cascades [ 20 ]. Thus, most efforts have been directed to inhibit the action of oncogenes [ 21 , 22 , 23 , 24 ], for instance, the development of selective K-Ras inhibitors [ 25 ]. In some of the recent studies, however, the other side of the oncogene actions has been revealed [ 26 , 27 ].…”