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[Multidrug or pleiotropic resistance]
F Arvelo1, E Merentes, C Cotte
1Laboratorio de Cultivo de Tejidos y Biología de Tumores, Facultad de Ciencias, U.C.V., Caracas, Venezuela.
Abstract:
The resistance to cytotoxic drugs represents a major obstacle to successful cancer therapy. The intrinsic resistance of tumoral cells is one of major causes of treatment failure. The overexpression of a membrane associated glycoprotein, P-glycoprotein, in tumoral cell lines, resistant to a wide range of drugs, permitted the description of a multidrug resistance (MDR) phenotype. This P-glycoprotein, which appears to play a role in drug efflux is encoded by the mdr1 gene in humans. The frequent mdr1 gene overexpression in clinically resistant tumours suggest that this gene may be the cause of treatment failure in human cancer. This review summarizes recent developments in this area, which suggest that both the activity of the pump and its genetic regulation are potential targets for new anticancer therapies.
Insights
Multidrug resistance (MDR) in cancer, often caused by P-glycoprotein (encoded by the mdr1 gene), is a major treatment obstacle. Targeting P-glycoprotein activity and mdr1 gene regulation offers new therapeutic strategies for overcoming cancer drug resistance.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Cytotoxic drug resistance in cancer is a significant barrier to effective treatment.
- Intrinsic resistance of tumor cells contributes to therapeutic failure.
- P-glycoprotein, a membrane glycoprotein, is associated with multidrug resistance (MDR) phenotype.
Purpose of the Study:
- To review recent developments concerning P-glycoprotein and the mdr1 gene in cancer drug resistance.
- To explore the role of P-glycoprotein in drug efflux.
- To identify potential therapeutic targets for overcoming MDR.
Main Methods:
- Review of scientific literature on P-glycoprotein, mdr1 gene, and multidrug resistance.
- Analysis of studies investigating the function of P-glycoprotein in drug-resistant cell lines and tumors.
- Examination of research on the genetic regulation of the mdr1 gene.
Main Results:
- P-glycoprotein overexpression is linked to MDR in various drug-resistant tumoral cell lines.
- The human mdr1 gene encodes P-glycoprotein, implicated in drug efflux.
- Frequent mdr1 gene overexpression in clinically resistant tumors suggests its role in treatment failure.
Conclusions:
- P-glycoprotein plays a crucial role in the multidrug resistance phenotype.
- The mdr1 gene's overexpression is a potential cause of treatment failure in human cancers.
- Modulating P-glycoprotein activity and mdr1 gene regulation presents promising avenues for novel anticancer therapies.