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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Small Molecule Drugs and Targeted Therapy for Melanoma: Current Strategies and Future Directions

Author(s): Carmen Cerchia and Antonio Lavecchia*

Volume 24, Issue 21, 2017

Page: [2312 - 2344] Pages: 33

DOI: 10.2174/0929867324666170414163937

Price: $65


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 pathway- 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.

Keywords: Melanoma, metastasis, small molecules, targeted therapies, drug-resistance, MAPK pathway, cell cycle control.

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