Journal
CURRENT MEDICINAL CHEMISTRY
Volume 24, Issue 21, Pages 2312-2344Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/0929867324666170414163937
Keywords
Melanoma; metastasis; small molecules; targeted therapies; drug-resistance; MAPK pathway; cell cycle control
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Malignant melanoma is the most aggressive and life-threatening skin cancer. Melanoma develops in melanocytes and is characterized by a very high tendency to spread to other parts of the body. Its pathogenesis depends on DNA mutations leading to the activation of oncogenes or to the inactivation of suppressor genes. The identification of misregulations in intracellular signal transduction pathways has provided an opportunity for the development of mutation-specific inhibitors, which specifically target the mutated signaling cascades. Over the last few years, clinical trials with MAPK pathway inhibitors have shown significant clinical activity in melanoma; however, their efficacy is limited due to the onset of acquired resistance. This has prompted a large set of preclinical studies looking at new approaches of path-way- or target-specific inhibitors. This review gives an overview of the latest developments of small molecule targeting multiple molecular pathways in both preclinical and clinical melanoma settings, with particular emphasis on additional strategies to tackle the reduced responsiveness to inhibitor treatment as possible future directions.
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