Abstract
The success of anticancer therapy is limited due to the resistance caused by tumor cells to cytotoxic agents, which interfere with the effectiveness of various chemotherapeutic agents. Several mechanisms for decreased effectiveness of anti-cancer drugs have been examined however the most widely studied mechanism is the efflux of cytotoxic drugs from the cell due to P-gp overexpression. However, the role of P-gp inhibitors in improving chemotherapy is limited due to the existence of other mechanisms of resistance such as activation of glutathione mediated detoxification, blockade of DNA repair, apoptotic pathways, TK signaling pathways and altered tumor microenvironment. Alternative strategies to overcome factors responsible for reduced efficacy of cancer therapy have also been considered such as inhibition of the detoxification system like glutathione, targeting Tks and DNA repair pathways, combination of angiogenic inhibitors, RNAi mediated inhibition of targeted genes etc. Additionally, preventing the onset of resistance can be targeted via siRNA strategy and nanoparticle strategy. In this review, we describe detailed mechanisms involved in decreasing effectiveness of anticancer drugs as well as the strategies used to modulate these mechanisms for effective cancer treatment.
Keywords: Angiogenesis, apoptotic pathways, cancer, DNA repair pathways, inhibitors, multidrug resistance, nanoparticle strategy, RNAi strategy, tyrosine kinases inhibitors.
Anti-Cancer Agents in Medicinal Chemistry
Title:Physiological Modulation Approaches to Improve Cancer Chemotherapy : A Review
Volume: 14 Issue: 5
Author(s): Rajesh Kumar, Maninder Kaur and Om Silakari
Affiliation:
Keywords: Angiogenesis, apoptotic pathways, cancer, DNA repair pathways, inhibitors, multidrug resistance, nanoparticle strategy, RNAi strategy, tyrosine kinases inhibitors.
Abstract: The success of anticancer therapy is limited due to the resistance caused by tumor cells to cytotoxic agents, which interfere with the effectiveness of various chemotherapeutic agents. Several mechanisms for decreased effectiveness of anti-cancer drugs have been examined however the most widely studied mechanism is the efflux of cytotoxic drugs from the cell due to P-gp overexpression. However, the role of P-gp inhibitors in improving chemotherapy is limited due to the existence of other mechanisms of resistance such as activation of glutathione mediated detoxification, blockade of DNA repair, apoptotic pathways, TK signaling pathways and altered tumor microenvironment. Alternative strategies to overcome factors responsible for reduced efficacy of cancer therapy have also been considered such as inhibition of the detoxification system like glutathione, targeting Tks and DNA repair pathways, combination of angiogenic inhibitors, RNAi mediated inhibition of targeted genes etc. Additionally, preventing the onset of resistance can be targeted via siRNA strategy and nanoparticle strategy. In this review, we describe detailed mechanisms involved in decreasing effectiveness of anticancer drugs as well as the strategies used to modulate these mechanisms for effective cancer treatment.
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Cite this article as:
Kumar Rajesh, Kaur Maninder and Silakari Om, Physiological Modulation Approaches to Improve Cancer Chemotherapy : A Review, Anti-Cancer Agents in Medicinal Chemistry 2014; 14 (5) . https://dx.doi.org/10.2174/18715206113136660364
DOI https://dx.doi.org/10.2174/18715206113136660364 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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