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Pharmacological Strategies for Overcoming Multidrug Resistance to Chemotherapy

T A Fedotcheva1, N L Shimanovsky1

  • 1Pirogov Russian National Research Medical University, Moscow, 1 Ostrovityanova St., 117997 Russia.

Pharmaceutical Chemistry Journal
|January 23, 2023
PubMed

Insights

Multidrug resistance (MDR) in cancer chemotherapy involves ABC-transporters. Fourth-generation inhibitors, like plant flavonoids, offer new strategies to overcome MDR by targeting these transporters.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Multidrug resistance (MDR) significantly limits chemotherapy efficacy in cancer treatment.
  • ATP-binding cassette (ABC) transporters, including P-glycoprotein, BCRP, and MRP proteins, are key mediators of MDR.
  • Understanding the mechanisms of MDR is crucial for developing effective cancer therapies.

Purpose of the Study:

  • To review the mechanisms of MDR in oncology.
  • To present the different generations of chemosensitizers, focusing on ABC transporter inhibitors.
  • To highlight the role of plant polyphenols (flavonoids) as fourth-generation MDR inhibitors.

Main Methods:

  • Literature review of existing research on MDR mechanisms and chemosensitizers.
  • Categorization of chemosensitizers into four generations based on their targets and development.
  • Analysis of the role of specific ABC transporters in conferring drug resistance.

Main Results:

  • Identified ABC-transporters as critical players in the development of MDR.
  • Described four generations of chemosensitizers, with a focus on ABC transporter inhibitors.
  • Highlighted plant polyphenols (flavonoids) as promising fourth-generation MDR inhibitors.

Conclusions:

  • Chemosensitizer selection should be tailored to individual patient mutation-expression profiles and tumor receptor status.
  • Optimizing the dosage and administration schedule of chemosensitizers can improve the effectiveness of overcoming MDR.
  • Targeting ABC transporters with novel chemosensitizers, including flavonoids, holds potential for enhancing cancer chemotherapy outcomes.
Keywords:
BCRP-proteinMRP proteinsP-glycoproteinflavonoidsmultidrug resistancetyrosine kinase inhibitors

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