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Review
. 2022 Dec;5(12):e1291.
doi: 10.1002/cnr2.1291. Epub 2020 Oct 13.

Molecular and cellular paradigms of multidrug resistance in cancer

Foram U Vaidya  1 , Abu Sufiyan Chhipa  1 , Vinita Mishra  1 , Vishal Kumar Gupta  2 , Shiv Govind Rawat  2 , Ajay Kumar  2 , Chandramani Pathak  1
Affiliations
Review

Molecular and cellular paradigms of multidrug resistance in cancer

Foram U Vaidya et al. Cancer Rep (Hoboken). 2022 Dec.

Abstract

Background: The acquisition of resistance to chemotherapy is a major hurdle in the successful application of cancer therapy. Several anticancer approaches, including chemotherapies, radiotherapy, surgery and targeted therapies are being employed for the treatment of cancer. However, cancer cells reprogram themselves in multiple ways to evade the effect of these therapies, and over a period of time, the drug becomes inactive due to the development of multi-drug resistance (MDR). MDR is a complex phenomenon where malignant cells become insensitive to anticancer drugs and attain the ability to survive even after several exposures of anticancer drugs. In this review, we have discussed the molecular and cellular paradigms of multidrug resistance in cancer.

Recent findings: An Extensive research in cancer biology revealed that drug resistance in cancer is the result of perpetuated intracellular and extracellular mechanisms such as drug efflux, drug inactivation, drug target alteration, oncogenic mutations, altered DNA damage repair mechanism, inhibition of programmed cell death signaling, metabolic reprogramming, epithelial mesenchymal transition (EMT), inherent cell heterogeneity, epigenetic changes, redox imbalance, or any combination of these mechanisms. An inevitable cross-link between inflammation and drug resistance has been discussed. This review provided insight molecular mechanism to understand the vulnerabilities of cancer cells to develop drug resistance.

Conclusion: MDR is an outcome of interplays between multiple intricate pathways responsible for the inactivation of drug and development of resistance. MDR is a major obstacle in regimens of successful application of anti-cancer therapy. An improved understanding of the molecular mechanism of multi drug resistance and cellular reprogramming can provide a promising opportunity to combat drug resistance in cancer and intensify anti-cancer therapy for the upcoming future.

Keywords: Cancer metabolism; Cellular reprogramming; Inflammation; Multi drug resistance and cancer; Programmed cell death; Tumor microenvironment.

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Conflict of interest statement

Authors are not having any conflict of interest.

Figures

FIGURE 1
FIGURE 1
Cellular and molecular events involved in the development of drug resistance in cancer
FIGURE 2
FIGURE 2
Domain structural organization of ABCB1, ABCC1, and ABCG2. Sequences and their domain information were retrieved from Uniprot Database and domains were created with Illustrator of Biological Sequences (IBS). TM, Transmembrane region; NBD, Nucleotide Binding Domain
FIGURE 3
FIGURE 3
Interaction of ABCB1, ABCC1 and ABCG2 with the genes that are involved in cancer pathology. Interaction map was created with STRING database. The network and Molecular action view of protein‐protein interactions (by their gene name) were created by STRING version 11.0 with high confidence (0.700) and custom value for numbers of interactions were set to 50. Modes of action are shown in different colors
See this image and copyright information in PMC

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