Title:Genetic and Epigenetic Modulation of Drug Resistance in Cancer: Challenges and Opportunities
Volume: 20
Issue: 14
Author(s): Kanisha Shah and Rakesh M. Rawal*
Affiliation:
- Department of Life Science, School of Sciences, Gujarat University, Navrangpura, Ahmedabad, Gujarat 380009,India
Keywords:
Drug response, resistance mechanisms, epigenetics, microRNAs, epithelial-mesenchymal transitions, drug target alteration.
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.