Cyclophilin A as a Target of Cisplatin Chemosensitizers.

Cyclophilin A as a Target of Cisplatin Chemosensitizers. Curr Cancer Drug Targets. 2013 Nov 4; Authors: Hamilton G Abstract Platinum-based chemotherapeutics are the mainstay of treatment of a range of tumors achieving high response rates but limited in the course of disease by appearance of drug resistance. Tumor cells respond with reduced uptake and increased intracellular inactivation of the drugs, as well as increased DNA repair and general resistance to chemotherapy-induced cell death. Cisplatin is known to induce expression of cyclophilins, a group of proteins that have peptidyl-prolyl cis-trans isomerase (PPIase) and molecular chaperone activities, as stress response. Cyclophilin A (CypA) and other members of this family are inhibited by cyclosporin A (CsA) which sensitizeddiverse drug-resistant tumor cell lines in vitro to cisplatin. This effect of CsA was attributed to metabolic changes, inhibition of DNA repair, enhancement of apoptosis, altered intracellular signal transduction or increased production of reactive oxygen species (ROS), although no definitive explanation was provided so far. Several clinical trials employing cisplatin/carboplatin in combination with CsA yielded unsatisfactory results. Since viral replication was found to be dependent on cyclophilins of the host cells, effective new inhibitors,different from CsA or with low or absent immunosuppressive activity, are in the development or clinical trials. Sanglifehrins ar...
Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research