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A critical review on modulators of Multidrug Resistance Protein 1 in cancer cells

Vivian Osei Poku1, Surtaj Hussain Iram1,2

  • 1Department of Chemistry and Biochemistry, South Dakota State University, Brookings, SD, United States of America.

Peerj
|January 17, 2022
PubMed

Insights

Multidrug resistance protein 1 (MRP1) is a key efflux transporter implicated in cancer drug resistance and other diseases. Understanding MRP1 modulators is crucial for improving cancer treatment and patient outcomes.

Area of Science:

  • Biochemistry and Molecular Biology
  • Pharmacology
  • Oncology

Background:

  • Multidrug resistance protein 1 (MRP1/ABCC1) is an ATP-dependent efflux transporter critical for xenobiotic and drug transport across cell membranes.
  • MRP1 plays a vital role in drug disposition, including anticancer agents, antivirals, and antibiotics, influencing their efficacy and cellular barriers.
  • Overexpression of MRP1 is a significant clinical marker for multidrug resistance (MDR) in various cancers, leading to treatment failure and reduced survival rates.

Approach:

  • This review synthesizes current knowledge on the physiological and pharmacological roles of MRP1.
  • It examines known MRP1 modulators and their mechanisms of action.
  • The review also discusses existing challenges and future research directions for MRP1-targeted therapies.

Key Points:

  • MRP1's involvement extends beyond MDR to include physiological processes like redox homeostasis and steroid metabolism.
  • MRP1 overexpression is linked to neurodegenerative and cardiovascular diseases, highlighting its broader pathological relevance.
  • Identifying and characterizing MRP1 modulators is a key area of interest for cancer research and therapeutic development.

Conclusions:

  • Further research into MRP1 modulators holds significant potential for overcoming drug resistance in cancer.
  • Targeting MRP1 could offer novel therapeutic strategies for various diseases associated with its dysregulation.
  • A comprehensive understanding of MRP1's function and modulation is essential for advancing clinical treatments.
Keywords:
ABC transporterABCC1Anti-cancer agentsDrug absorption and dispositionDrug profilingDrug-transporter interactionsMRP1MRP1 modulatorsMultidrug Resistance

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