Targeting telomerase.
Given the constitutive expression of telomerase in the majority of human tumors, telomerase inhibition is an attractive, broad-spectrum therapeutic target for cancer treatment. Therapeutic strategies for inhibiting telomerase activity have included both targeting components of telomerase (the protein component, TERT, or the RNA component, TERC) or by directly targeting telomere DNA structures. Recently a combination telomerase inhibition therapy has been studied also. The TERT promoter has been used to selectively express cytotoxic gene(s) in cancer cells and a TERT vaccine for immunization against telomerase has been tested. The 10% to 15% of immortalized cancer cells that do not express telomerase use a recombination-based mechanism for maintaining telomere structures that has been called the alternative lengthening of telomeres (ALT). In view of the increasing study of telomerase inhibitors as anticancer treatments, it will be crucial to determine whether inhibition of telomerase will select for cancer cells that activate ALT mechanisms of telomere maintenance.
Siddiqa
Aisha
A
Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
Cavazos
David A
DA
Marciniak
Robert A
RA
D002471:Cell Transformation, Neoplastic; D016922:Cellular Senescence / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D012313:RNA / Q000378:metabolism / Q000627:therapeutic use; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use
D004268:DNA-Binding Proteins; C422952:telomerase RNA; D012313:RNA; C509186:TERT protein, human; D019098:Telomerase