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Non P-glycoprotein novel proteins involved in human cancer multidrug resistance
1Institut de biologie et chimie des protéines, UPR 412 CNRS, Lyon, France.
Abstract:
Multidrug resistance of cancer cells is a serious problem in the treatment of tumors and is the leading cause of the frequent failure of chemotherapy. Cancer cell chemoresistance is based on the development of several mechanisms among which one of the most important concerns the overexpression of membrane proteins to remove cytotoxic compounds from the cytoplasm. The leading archetype of these proteins is the P-glycoprotein, a member of the ATP-binding cassette (ABC) superfamily of transporters, or traffic ATPases. In the recent past years, new non P-glycoprotein membrane proteins, several of which being members of the ABC superfamily of transporters, and new genes, have been discovered in cancer cells with a multiple drug resistance phenotype. In this article, we briefly review these newly discovered entities.
Insights
Multidrug resistance in cancer, often due to P-glycoprotein and other ATP-binding cassette transporters, frequently causes chemotherapy failure. This review highlights newly discovered membrane proteins and genes contributing to this chemoresistance.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Multidrug resistance (MDR) in cancer cells is a significant clinical challenge, leading to chemotherapy failure.
- A primary mechanism of MDR involves the overexpression of membrane proteins that efflux cytotoxic drugs from cancer cells.
- P-glycoprotein, an ATP-binding cassette (ABC) transporter, is a well-established mediator of this drug efflux.
Purpose of the Study:
- To review newly discovered membrane proteins and genes associated with multidrug resistance in cancer.
- To highlight emerging mechanisms beyond P-glycoprotein in cancer cell chemoresistance.
Main Methods:
- Literature review of recent scientific publications.
- Analysis of studies identifying novel membrane proteins and genes in multidrug-resistant cancer cells.
- Focus on ATP-binding cassette (ABC) superfamily transporters and other efflux pumps.
Main Results:
- Identification of novel, non-P-glycoprotein membrane proteins implicated in MDR.
- Discovery of new genes contributing to the multidrug resistance phenotype in various cancers.
- Confirmation that ABC transporters, beyond P-glycoprotein, play a crucial role in MDR.
Conclusions:
- Emerging membrane proteins and genes, including additional ABC transporters, are critical players in cancer multidrug resistance.
- Understanding these novel entities is essential for developing strategies to overcome chemotherapy resistance.
- Further research into these newly discovered resistance mechanisms is warranted.