Targeting the telosome: therapeutic implications.
Since telomere integrity is required to guarantee the unlimited replicative potential of cancer cells, telomerase, the enzyme responsible for telomere length maintenance in most human tumors, and lately also telomeres themselves have become extremely attractive targets for new anticancer interventions. At the current status of knowledge, it is still not possible to define the best therapeutic target between telomerase and telomeres. It is noteworthy that interfering with telomeres, through direct targeting of telomeric DNA or proteins involved in the telosome complex, could negatively affect the proliferative potential not only of tumors expressing telomerase activity but also of those that maintain their telomeres through alternative lengthening or still unknown mechanisms. This review presents the different therapeutic approaches proposed thus far and developed in preclinical tumor models and discusses the perspectives for their use in the clinical setting.
Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy.
Marco
M
Folini
Paolo
P
Gandellini
Nadia
N
Zaffaroni
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*
D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D019098:Telomerase