[Antitumor drug resistance and therapeutic approaches to reverse resistance].
Acquired multidrug resistance as well as innate drug resistance are directly related to ineffectiveness and failure of the cancer chemotherapy. The mechanisms of such resistance, especially those of innate resistance, have not been fully elucidated. Drug resistant tumor cells, however, usually bear biochemical changes which are related to resistance mechanisms. New modalities with high selectivity against resistant cells could, therefore, be possible if we could target these biochemical changes. Vincristine (VCR)-and adriamycin (ADM)-resistant tumor cells (pleiotropic drug resistant cells) usually show an enhanced outward transport of these antitumor agents, and they express unique glycoproteins in the plasma membrane. By targeting for these biochemical changes characteristic to the resistant tumor cells, we establish new modality which shows high selectivity against drug resistant tumor cells. In this review, I will describe genetic origin of drug resistance, biochemical mechanisms of drug resistance and reversal of drug resistance in tumor cells. The modality to utilize calcium channel blockers which inhibit the enhanced outward transport of VCR and ADM from resistant tumor cells will be reviewed.
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002869:Chromosome Aberrations; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D004357:Drug Synergism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D013489:Suppression, Genetic / Q000187:drug effects; D014750:Vincristine / Q000494:pharmacology
D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D014750:Vincristine; D004317:Doxorubicin