Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemotherapy for advanced ovarian cancer remains suboptimal. Despite the improvements in objective response rates realized with cisplatin-based combination chemotherapeutic regimens, most patients still die of refractory cancer. Drug resistance has emerged as the single most important determinant of treatment outcome. Laboratory studies have provided substantial insights into the cellular mechanisms of resistance to the commonly used chemotherapeutic agents. Decreased drug accumulation, metabolic drug inactivation, and repair or tolerance to drug-induced cellular injury all contribute to resistance at the cellular level. Identification of these mechanisms has facilitated the development of specific treatment strategies, many of which are in or nearing clinical trials. These strategies include dose intensification, inhibition of P-glycoprotein function, inhibition of cellular glutathione synthesis, and inhibition of cellular DNA repair. The initial results from clinical trials that use these strategies provide reasonable grounds for optimism. In addition, efforts to identify new drugs with activity against resistant cells continue. One such drug, taxol, has significant activity in tumors refractory to conventional therapy. These approaches offer hope that intensive laboratory and clinical efforts ultimately will translate into real improvements in the efficacy of chemotherapy for ovarian cancer.
 ...
PMID:Mechanisms and modulation of resistance to chemotherapy in ovarian cancer. 809 21

Multidrug resistance (MDR) is a major hindrance to the successful treatment of neoplastic disease. The development of resistance to multiple chemotherapeutic drugs is a complex phenomenon which has been described in both tumor cell lines and human cancers. To date, two mechanisms associated with overexpression of membrane glycoproteins that function as energy-dependent efflux pumps to reduce intracellular drug levels have been identified for MDR. The first described was the product of the MDR1 gene, P-glycoprotein. The second mechanism is mediated by overexpression of the multidrug resistance-associated protein (MRP). While these proteins both belong to the ATP-binding cassette superfamily of transporters, they are only distantly related. Despite this low homology, they mediate resistance to a similar range of chemotherapeutic drugs. While P-glycoprotein has been well described in the literature, much less is known about the recently identified MRP. This review gives an overview of the characteristics of MRP at both the phenotypic and genotypic levels, and discusses its possible relevance in drug-refractory cancer.
 ...
PMID:The role of multidrug resistance-associated protein (MRP) expression in multidrug resistance. 914 6