chapter  4
24 Pages

Cancer C ell M etabolism and M ultidrug Resistance (MDR)

M ultidrug resistance (MDR) of cancer cells is a sim ultaneous resistance of tum or cells to m ultiple cytotoxic drugs, is a com plex or m ultiplex phenom enon w hose m olecular and m etabolic m echanism s are not yet fully understood and w hich is the m ajor obstacle and lim itation to the successful chem otherapeutic treatm ent of cancer (1-3). A lthough the genetic and biochem ical alterations responsible for the M D R phenotype of cancer cells have been the subject of intense investigations in the last 2 -3 decades, the cellular and m olecular m echanism s of action are not yet fully elucidated. However, significant progress has been m ade in the understand­ ing of m ultidrug resistance associated genes, proteins, antibodies and enzym es involved in the M D R m echanism of action. Thus, a better understanding and cir­ cum venting of m ultidrug resistance is a high priority for cancer chem otherapy (4). M D R is a com m on phenom enon due to cross resistance betw een different cytotox­ ic drugs w hich are structurally and functionally different. Investigations w ith can­ cer cell lines and cancer specim ens obtained from patients have show n that cross resistance betw een different cytotoxic drugs that are structurally and m echanical­ ly dissim ilar is a com m on phenom enon. It is w ell know n that M D R m ay be pre­ sent before treatm ent called "intrinsic or innate drug resistance" (renal and colon cancers) or can develop during treatm ent (chem otherapy, radiation therapy or horm one therapy) and called "acquired drug resistance" (lym phom as and breast cancers). M ultidrug resistance (MDR) is a com plex and m ultifactorial phenom e­ non and its m echanism (s) of action are nam ely due to (1) reduced intracellular drug accum ulation, (2) altered intracellular distribution and (3) increased efflux of cytotoxic drugs (4-7).