Abstract
Metastatic melanoma is one of the most intractable tumors, with all current regimens showing limited survival impact. Failure of most agents is attributed to development of therapy resistance. Accumulated evidence points to the apoptotic defect of melanoma cells and the surge of survival signals stimulated by cytotoxic drugs, as a way that tumors circumvent cytotoxic chemotherapy. An overview of inhibitors developed against these growth/survival factors, which are potential partners to be combined with systemic chemotherapy, will be discussed. The escape mechanism from molecular inhibitors also suggests a “vertical” or “horizontal” combination of molecularly targeted therapies. A better understanding of the interactions between simultaneously used regimens and of the rationale for combination therapy will provide new insights to improve survival and quality of life in patients with advanced melanoma.
Keywords: Melanoma, chemotherapy, drug resistance, targeted therapy, radiation, immunotherapy, dacarbazine, dartmouth regimen, biologics, tremelimumab, ipilimumab, BRAF inhibitor PLX4032, tumor cells, cancer therapy, chemotherapeutic agents
Current Molecular Medicine
Title: Resistance to Chemotherapy and Molecularly Targeted Therapies: Rationale for Combination Therapy in Malignant Melanoma
Volume: 11 Issue: 7
Author(s): S. Wu and R.K. Singh
Affiliation:
Keywords: Melanoma, chemotherapy, drug resistance, targeted therapy, radiation, immunotherapy, dacarbazine, dartmouth regimen, biologics, tremelimumab, ipilimumab, BRAF inhibitor PLX4032, tumor cells, cancer therapy, chemotherapeutic agents
Abstract: Metastatic melanoma is one of the most intractable tumors, with all current regimens showing limited survival impact. Failure of most agents is attributed to development of therapy resistance. Accumulated evidence points to the apoptotic defect of melanoma cells and the surge of survival signals stimulated by cytotoxic drugs, as a way that tumors circumvent cytotoxic chemotherapy. An overview of inhibitors developed against these growth/survival factors, which are potential partners to be combined with systemic chemotherapy, will be discussed. The escape mechanism from molecular inhibitors also suggests a “vertical” or “horizontal” combination of molecularly targeted therapies. A better understanding of the interactions between simultaneously used regimens and of the rationale for combination therapy will provide new insights to improve survival and quality of life in patients with advanced melanoma.
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Cite this article as:
Wu S. and Singh R.K., Resistance to Chemotherapy and Molecularly Targeted Therapies: Rationale for Combination Therapy in Malignant Melanoma, Current Molecular Medicine 2011; 11 (7) . https://dx.doi.org/10.2174/156652411800615153
DOI https://dx.doi.org/10.2174/156652411800615153 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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