Overcoming cancer multidrug resistance through inhibition of microparticles

Abstract

One of the main obstacles to success of chemotherapy agents is the development of cancer resistance. Cancer multi-drug resistance (MDR) is thought to arise from over-expression of efflux transporters on cancer cells’ plasma membranes. Recently, microparticles (MP) were found to play a major role in mediating the resistance to antineoplastic agents. Microparticles can confer MDR phenotype to cancer cells though 3 complimentary pathways: 1) Intercellular transfer of P-gp and MRP1; 2) Intercellular transfer of regulatory nucleic acids that ensure acquisition of MDR phenotype; and 3) Internal sequestration of anticancer drugs to reduce the amount of free active drug. Compounds that inhibit MP formation that are currently under investigation include calpain inhibitors, RhoA inhibitors, ROCK inhibitors, calcium channel blockers, pantethine, glutaminase inhibitors, some anti-platelet drugs and some lipid-lowering agents. This area of research requires further development to select, improve and test those compounds that show the most promise in providing safe and effective treatment against MDR.