What is the P-glycoprotein role in multi drug resistant cancers?
P-glycoprotein (P-gp) is a key player in the multidrug-resistant phenotype in cancer. The protein confers resistance by mediating the ATP-dependent efflux of an astonishing array of anticancer drugs.
How do you think this overexpression of P-glycoprotein may have happened?
However, overexpression of P-gp may be induced by selection and/or adaptation of cells during exposure to anticancer drugs; this particular example is known as acquired P-gp-mediated MDR. Drugs that are potential inducers of P-gp are often substrates of this transporter.
Which of the following chemotherapeutics are affected by the Multi Drug Resistant P-glycoprotein pump?
Abbreviations Used
| MDR | multidrug resistance |
|---|---|
| ABC | ATP-binding cassette |
| MRP1 | MDR-associated protein 1 |
| BCRP | breast cancer resistance protein |
| TM | transmembrane |
What is the glycoprotein that is most commonly associated with multidrug resistance?
P-glycoprotein (P-gp) is a membrane protein associated with multidrug resistance (MDR) due to its key role in mediating the traffic of chemotherapeutic drugs outside cancer cells, leading to a cellular response that hinders efforts toward successful therapy.
What is the role of P-glycoprotein?
P-glycoprotein is one of the drug transporters that determine the uptake and efflux of a range of drugs. P-glycoprotein functions as a transmembrane efflux pump, pumping its substrates from inside to outside the cell. Drugs which induce or inhibit P-glycoprotein can interact with other drugs handled by the pump.
What does P-glycoprotein do?
P-glycoprotein, the most extensively studied ATP-binding cassette (ABC) transporter, functions as a biological barrier by extruding toxins and xenobiotics out of cells. In vitro and in vivo studies have demonstrated that P-glycoprotein plays a significant role in drug absorption and disposition.
Where is P-glycoprotein found?
P-gp is primarily found in epithelial cells which have the excretory roles including apical surface of epithelial cells lining the colon, small intestine, pancreatic ductules, bile ductules, kidney proximal tubules, and the adrenal gland. It is also located in the endothelial cells of the blood brain barrier (BBB).
What is the role of P-glycoprotein on pharmacokinetic aspects?
What is the role of P-glycoprotein in cancer?
Development of multidrug resistance (MDR) still remains a major obstacle to the long-term success of cancer therapy. P-glycoprotein (P-gp) is a well-identified membrane transporter with capability to efflux drug molecules out of the cancer cell leading to reduced efficiency of chemotherapy.
Why do cancer cells upregulate P-gp expression?
Cancer cells upregulate P-gp expression as an adaptive response to evade chemotherapy mediated cell death. While several P-gp inhibitors have been discovered by in silico and pre-clinical studies, very few have successfully passed all phases of the clinical trials.
Are there any P-gp inhibitors for cancer?
While several P-gp inhibitors have been discovered by in silico and pre-clinical studies, very few have successfully passed all phases of the clinical trials. Studies show that application of P-gp inhibitors in cancer therapy regimen following development of MDR achieved limited beneficial outcomes.
Is there a negative correlation between P-gp and drug sensitivity?
Their results have demonstrated that more than 95% of the compounds exerted a negative correlation between drug sensitivity and P-gp expression.