Resistance against clinically approved anticancer drugs is the main roadblock in
cancer treatment.
Drug metabolizing
enzymes (
DMEs) that are capable of metabolizing a variety of
xenobiotic get overexpressed in malignant cells, therefore, catalyzing
drug inactivation. As evident from the literature reports, the levels of
DMEs increase in
cancer cells that ultimately lead to
drug inactivation followed by drug resistance. To puzzle out this issue, several strategies inclusive of analog designing,
prodrug designing, and inhibitor designing have been forged. On that front, the implementation of computational tools can be considered a fascinating approach to address the problem of chemoresistance. Various research groups have adopted different molecular modeling tools for the investigation of
DMEs mediated toxicity problems. However, the utilization of these in-silico tools in maneuvering the DME mediated chemoresistance is least considered and yet to be explored. These tools can be employed in the designing of such chemotherapeutic agents that are devoid of the resistance problem. The current review canvasses various molecular modeling approaches that can be implemented to address this issue. Special focus was laid on the development of specific inhibitors of
DMEs. Additionally, the strategies to bypass the
DMEs mediated
drug metabolism were also contemplated in this report that includes analogs and
pro-drugs designing. Different strategies discussed in the review will be beneficial in designing novel chemotherapeutic agents that depreciate the resistance problem.