Resistance to apoptosis in prostate cancer cells

S. B. Howell, N. Bruchovsky, M. Garzotto, L. Klotz

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Androgen-independent prostate cancer cells are remarkably resistant to therapeutic agents that work by triggering apoptosis via the caspase cascade. The recent sequencing of the entire genome of one of the most radiation-resistant organisms known, Deinococcus radiodurans, yields some insight into how prostate cancer cells might mount such resistance to apoptosis. Rather than being attributable to any one mechanism, the extreme radiation resistance of D. radiodurans appears to reflect the expression of a large number of different systems capable of preventing, repairing, or tolerating DNA damage and a very high degree of redundancy in these systems. Many molecular alterations that may influence the threshold for apoptosis have already been described in advanced prostate cancer; changes in bcl-2, p53, and the androgen receptor have been the most extensively studied. Current information is consistent with the concept that individual prostate cancer cells express multiple antiapoptotic mechanisms. This conclusion implies that it will not be possible to enhance cellular sensitivity to therapeutics that activate apoptosis by disabling just one target in a pathway, because other proteins are likely to be available to assume its function. Likewise, even elimination of a whole pathway may have little effect on sensitivity because cellular viability is protected by so many different mechanisms. However, where molecular changes have a phenotypic consequence, they offer a window of opportunity for the development of novel therapeutic strategies. One such example is a recently identified small organic compound that can inhibit p53 function and thus protect normal tissues against radiation-induced apoptosis without impairing killing of p53-deficient tumor cells.

Original languageEnglish (US)
Pages (from-to)225-229+231
JournalMolecular Urology
Issue number3
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Urology


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