Senescence Induction as a Possible Cancer Therapy
Lleonart ME, Artero-Castro A, Kondoh H. Senescence induction; a possible cancer therapy. Mol Cancer. 2009 Jan 8;8(1):3. PMID: 19133111
In normal cells, the ends of chromosomes (telomeres) tend to become shortened with each cell division. When telomeres shorten to a certain length, the cell can no longer replicate and enters senescence. In many cancer cells, a protein normally present in fetal development but not in adults (telomerase) maintains the length of telomeres, effectively conferring immortality. [See CancerQuest for a full explanation, with visuals.]
In Molecular Biology, authors from Fundació Institut de Recerca Hospital Vall d´Hebron in Barcelona and the Graduate School of Medicine, Kyoto University, describe telomerase inhibition and senescence induction as potential strategies for the development of novel cancer therapies. From the paper:
“Cellular senescence has become an attractive therapeutic concept because [it] mimics programmed cell death by excluding cells from active progression through the cell cycle. As an intact apoptotic machinery is unavailable in most established malignancies, a senescence-induced mechanism emerges as a back-up program to substitute for or to reinforce an insufficient apoptotic response. Importantly, the therapeutic potential of senescence induction strongly relies on the irreversibility of this process. Although, it has not been formally tested whether drug-inducible senescence is a complete[ly] reversible process, the acquisition of spontaneous mutations that disable p53 or pRB in a resting cell without DNA replication seems rather unlikely. Thereby it would be very interesting for preclinical investigations to explore future therapies which directly prompt a clear senescence response as those observed in vitro. It would be tempting to speculate that the combination of a senescence induced therapy and a conventional therapy might cooperate to entirely abolish cancer."
[OncologyWatch directory of open-access oncology journals.]
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