Volume 8, Issue 11 p. 1751-1765
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Targets, Structures, and Recent Approaches in Malignant Melanoma Chemotherapy

Ana Marta Matos

Ana Marta Matos

Research Institute for Medicines and Pharmaceutical Sciences (i Med. UL), Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon (Portugal)

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Dr. Ana Paula Francisco

Corresponding Author

Dr. Ana Paula Francisco

Research Institute for Medicines and Pharmaceutical Sciences (i Med. UL), Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon (Portugal)

Research Institute for Medicines and Pharmaceutical Sciences (i Med. UL), Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon (Portugal)Search for more papers by this author
First published: 16 August 2013
Citations: 7

Graphical Abstract

Targeting malignancies: Discovery of the pathophysiological processes behind malignant metastatic melanoma has allowed the development of novel drugs that are selective for several molecular targets. Such drugs may lead to increased survival rates and improved quality of life for cancer patients. Identifying the best molecular targets should lay the groundwork for developing new effective chemotherapies.

Abstract

Malignant metastatic melanoma is one of the oncologic diseases with the worst clinical prognosis, due primarily to resistance phenomena against chemotherapeutic agents in current use. However, over the last few years, characterization of the molecular mechanisms involved in the development and progression of the disease has contributed to elucidation of the main pathways by which tissue invasion and metastasis can occur. More importantly, the identification of abnormalities in signaling cascades in melanoma cells has facilitated new therapeutic approaches against malignant melanoma through the design of highly potent and selective drugs with low associated toxicity. Ultimately, recognition of the restricted applicability of new chemotherapies in certain genetic contexts has led to significant improvements in the results of clinical trials, anticipating the existing need for investment in personalized therapies, and taking into account the molecular alterations observed in tumors. Although significant advances have been made in terms of extending the median overall survival rate and improving the quality of life for patients, the mechanisms that compromise in vivo drug efficacy remain poorly understood, particularly those concerning therapeutic resistance phenomena. This review summarizes recently validated targets from the perspective of the medicinal chemistry carried out in the design of the most promising structures.