LIFE 210 Lecture Notes - Multiple Drug Resistance, P-Glycoprotein, Imatinib
Document Summary
Blood cancers and malignant/metastatic cancers (~50%) are treated with chemotherapy (not localized) Some patients are cured, but some do not respond due to drug resistant cancers. Drug resistant cancer arises through a range of mechanisms. Drug target changes, like bcr-abl protein catalytic site changes that affect gleevec binding affinity. More general multidrug resistant (mdr), conferring resistance to several drugs. Impaired drug delivery concentration in blood and tumor. Decreased cell uptake by transporters (polar drugs) transporters of nonpolar drugs) Increased cell export by atp-dependent pumps (abc family of. The binding site is in the lipid bilayer hydrophobic core. Its normal functions are protective, keeping toxins out. Pumps in cell (pgp) would get rid of dye. Pgp highly/over expressed in colon, kidney, adrenal, liver and blood cancer cells. Pgp levels are increased in breast cancer cells after chemotherapy. Pgp levels are also high in putative cancer stem cells . Pgp inhibitors are being developed to reduce mdr.
