[Telomere and telomerase as targets for anti-cancer drugs].
Telomerase is a hopeful molecular target of anti-cancer drugs because it is practically specific and essential for survival and growth of cancer cells. Cancer cells in vitro ceased proliferation after introduction of dominant-negative cDNA or RNAi of telomerase catalytic subunit (hTERT) or anti-sense RNA of template RNA subunit (hTR) of telomerase. Some reverse-transcriptase inhibitors, compounds that stabilize G-quartet structure of telomere DNA and other natural or synthetic compounds were reported to inhibit telomerase activity and proliferation of cancer cells in vitro. Vectors carrying cDNA that produces mutant hTR partly blocked proliferation of cancer cells probably through inhibition of sequence-specific binding of telomere proteins. Telomere binding proteins are possible targets of anti-cancer drugs that modify telomere structure and block recruitment of telomerase. Combination of inhibitors with different action mechanisms accelerated telomere shortening and reduced period of time required for cancer cell killing. Repressor of hTERT expression, menin, is a possible target in future.
Graduate School of Biomedical Sciences, Hiroshima University.
Toshinori
T
Ide
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics; D016615:Telomere / Q000187:drug effects*
D000970:Antineoplastic Agents; D019098:Telomerase