Sunday November 22 2009 | Biotechnology feed | All feeds
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Sunday November 22 2009 | Biotechnology feed | All feeds
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Survivin a candidate for cancer-specific apoptotic- and immuno-therapies Cancer is generally associated with reduced rates of apoptotic cell death and also alterations in the cell cycle. Thus, cell cycle inhibitors and pro-apoptotic molecules represent two classes of drug with considerable promise. For a while it has been known that a family of “Inhibitors of apoptosis” (IAPs) are expressed in tumors suppressing apoptosis through direct caspase and pro-caspase inhibition (primarily caspase 3 and 7) and modulation of and by the transcription factor NF-kappaB. Survivin presents the strongest evidence for IAP involvement in cancer. Although not observed in adult differentiated tissue, this IAP is present in most transformed cell lines and cancers tested to date. Even more importantly, survivin expression appears to be homogenous within the tumor environment, a feature unusual in a disease characterized by spontaneous mutation. Survivin has been shown to inhibit caspase directly and apoptosis in general, moreover survivin protein levels correlate inversely with 5-year survival rates in colorectal cancer. Thus there is considerable hope that targeting survivin could sensitize tissue to chemo- or radio-therapeutic treatment. A recent article raises the possibility that survivin also represents a target for vaccines and targeted immunotherapies. The field of “intracellular antibody capture” has been identified in previous editions of TherapeuticAdvances as a promising technology. This allows the targeting of intracellular antigens and survivin represents a potential area in which this exciting technology could be applied, either in an attempt to neutralize survivin or to target survivin with toxins or isotopes. Further, a combination of neutralization and targeted immunotherapy could offer synergistic activity since the former would sensitize cells to the pro-apoptotic activity of the latter. Link to journal abstract:
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