4.7 Article

Cancer multidrug-resistance reversal by ABCB1 inhibition: A recent update

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ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2022.114542

关键词

Multidrug-resistance; Efflux pumps; ABC efflux; ABCB1; P-gp1 efflux pump; ABCC1; ABCG2; Clinical trials; Drug repurposing; Nano formulation

资金

  1. NIPER Hyderabad

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Chemotherapy is a common treatment for cancer, but its drawbacks include lack of selectivity and development of drug resistance. Multidrug resistance refers to low sensitivity of specific cells to anticancer drugs, which is mainly caused by overexpression of multidrug efflux systems.
Chemotherapy is one of the most common treatments for cancer that uses one or more anti-cancer drugs as a part of the standardized chemotherapy regimen. Cytotoxic chemicals delay and prevent cancer cells from multiplying, invading, and metastasizing. However, the significant drawbacks of cancer chemotherapy are the lack of selectivity of the cytotoxic drugs to tumour cells and normal cells and the development of resistance by cells for the particular drug or the combination of drugs. Multidrug resistance (MDR) is the low sensitivity of specific cells against drugs associated with cancer chemotherapy. The most common mechanisms of anticancer drug resistance are: (a) drug-dependent MDR (b) target-dependent MDR, and (c) drug target-independent MDR. In all the factors, the overexpression of multidrug efflux systems contributes significantly to the increased resistance in the cancer cells. Multidrug resistance due to efflux of anticancer drugs by membrane ABC transporters includes ABCB1, ABCC1, and ABCG2. ABCB1 inhibition can restore the sensitivity of the cancerous cells toward chemotherapeutic drugs. In this review, we discussed ABCB1 inhibitors under clinical studies with their mode of action, potency and selectivity. Also, we have highlighted the contribution of repurposing drugs, biologics and nano formulation strategies to combat multidrug resistance by modulating the ABCB1 activity.

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