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Multidrug resistance in cancer (review)

R Srivastava1, A Srivastava, Y Chochung

  • 1NCI,CELLULAR BIOCHEM SECT,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892.

International Journal of Oncology
|May 5, 2011
PubMed

Insights

Cancer cells develop resistance to drugs via P-glycoprotein, a drug efflux pump. Protein kinases regulate this pump, offering potential targets to reverse multidrug resistance and improve chemotherapy efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Anticancer drug resistance is a significant challenge in cancer chemotherapy.
  • P-glycoprotein (P-gp) overexpression in cancer cells confers a multidrug resistance (MDR) phenotype.
  • P-gp functions as an efflux pump, reducing intracellular drug concentration and cytotoxicity.

Purpose of the Study:

  • To explore the role of protein kinases in modulating P-glycoprotein activity and MDR.
  • To investigate kinase-mediated phosphorylation and transcriptional regulation of P-gp.
  • To identify potential therapeutic strategies for reversing MDR and enhancing anticancer drug efficacy.

Main Methods:

  • Review of existing studies on protein kinase activators/inhibitors and P-glycoprotein.
  • Analysis of research on the phosphorylation of P-glycoprotein.
  • Examination of studies investigating the transcriptional regulation of the MDR1 gene by kinases.

Main Results:

  • Protein kinase activators and inhibitors can modulate P-glycoprotein activity, often through phosphorylation.
  • Some kinase modulators affect drug accumulation in MDR cells independently of their effects on P-gp phosphorylation.
  • Protein kinase A (PKA) and protein kinase C (PKC) are implicated in the transcriptional regulation of the MDR1 gene.

Conclusions:

  • Protein kinases are critical regulators of P-glycoprotein function and expression.
  • Targeting these kinases presents a promising strategy for overcoming multidrug resistance in cancer.
  • Further research into kinase pathways may lead to novel approaches to enhance anticancer drug effectiveness.

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