To Biochemically Trick P-Glycoprotein (Pgp) To Target Resistance Via Lysosomal Pgp
Funder
National Health and Medical Research Council
Funding Amount
$603,848.00
Summary
We have discovered an innovative biochemical strategy whereby our novel compounds exploit and trick a part of the detoxification machinery, that is the transporter, P-glycoprotein, to specifically kill drug resistant cancer cells. Herein, we take advantage of this biochemical mechanism to design novel and safe drugs to selectively target resistant tumours.
Microparticles And Selective Trait Dominance In Multidrug Resistant Cancers
Funder
National Health and Medical Research Council
Funding Amount
$478,115.00
Summary
Multidrug resistance (MDR) is the cause of treatment failure in 90% of patients with metastatic cancer. We recently discovered a novel resistance mechanism in which microparticles provide a vehicle for intercellular transfer of MDR. We now report that MP play an even more significant role in conferring MDR, by the ñre-templatingî of cancer cell traits. This has considerable potential for translation into clinical outcomes with the identification of alternative drug targets and therapeutics for t ....Multidrug resistance (MDR) is the cause of treatment failure in 90% of patients with metastatic cancer. We recently discovered a novel resistance mechanism in which microparticles provide a vehicle for intercellular transfer of MDR. We now report that MP play an even more significant role in conferring MDR, by the ñre-templatingî of cancer cell traits. This has considerable potential for translation into clinical outcomes with the identification of alternative drug targets and therapeutics for the circumvention of MDR clinically.Read moreRead less
Understanding Multidrug Resistance In Cancer: Identification Of The Substrate And Inhibitor Binding Sites In P-glycoprotein
Funder
National Health and Medical Research Council
Funding Amount
$284,343.00
Summary
Cancers expressing the multidrug transporter P-glycoprotein (P-gp) are resistant to chemotherapy. The clinical impact of P-gp is so large that the National Cancer Institute (USA) “profiles” all anticancer drugs for transport by P-gp, primarily because the mechanism of drug binding and transport by P-gp is unknown. The aim of this proposal is to understand the molecular details of how drugs bind to and interact with P-gp, a major step in our understanding of P-gp mediated chemotherapy resistance.
Role Of Flavonoids From Phytomedicines In Herb-Drug Interactions Mediated By P-glycoprotein
Funder
National Health and Medical Research Council
Funding Amount
$210,990.00
Summary
The herbal therapeutics St John's wort and Ginkgo biloba are used by cancer patients to alleviate symptoms of psychic disturbances associated with their condition. The possibility of interactions between flavonoid components of these herbs and anticancer treatment will be examined. Resistance to cancer chemotherapy often develops due to overexpression of the drug transporter P-glycoprotein (P-gp). Investigation of the interaction of the flavonoid components of herbal preparations and P-gp will e ....The herbal therapeutics St John's wort and Ginkgo biloba are used by cancer patients to alleviate symptoms of psychic disturbances associated with their condition. The possibility of interactions between flavonoid components of these herbs and anticancer treatment will be examined. Resistance to cancer chemotherapy often develops due to overexpression of the drug transporter P-glycoprotein (P-gp). Investigation of the interaction of the flavonoid components of herbal preparations and P-gp will establish whether the flavonoids alter the outcome of chemotherapy in resistant cancers in the short term. We will also examine whether exposure to flavonoids in herbal medicines and diets rich in flavonoids from fruit and vegetables affects development and progress of multidrug resistance over the long term.Read moreRead less