Genetic and Epigenetic Modulation of Drug Resistance in Cancer: Challenges and Opportunities

Author(s): Kanisha Shah, Rakesh M. Rawal*.

Journal Name: Current Drug Metabolism

Volume 20 , Issue 14 , 2019


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Abstract:

Cancer is a complex disease that has the ability to develop resistance to traditional therapies. The current chemotherapeutic treatment has become increasingly sophisticated, yet it is not 100% effective against disseminated tumours. Anticancer drugs resistance is an intricate process that ascends from modifications in the drug targets suggesting the need for better targeted therapies in the therapeutic arsenal. Advances in the modern techniques such as DNA microarray, proteomics along with the development of newer targeted drug therapies might provide better strategies to overcome drug resistance. This drug resistance in tumours can be attributed to an individual’s genetic differences, especially in tumoral somatic cells but acquired drug resistance is due to different mechanisms, such as cell death inhibition (apoptosis suppression) altered expression of drug transporters, alteration in drug metabolism epigenetic and drug targets, enhancing DNA repair and gene amplification. This review also focusses on the epigenetic modifications and microRNAs, which induce drug resistance and contributes to the formation of tumour progenitor cells that are not destroyed by conventional cancer therapies. Lastly, this review highlights different means to prevent the formation of drug resistant tumours and provides future directions for better treatment of these resistant tumours.

Keywords: Drug response, resistance mechanisms, epigenetics, microRNAs, epithelial-mesenchymal transitions, drug target alteration.

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Article Details

VOLUME: 20
ISSUE: 14
Year: 2019
Page: [1114 - 1131]
Pages: 18
DOI: 10.2174/1389200221666200103111539
Price: $58

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