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Prostate cancer


Cell culture and mouse studies suggest g-secretase inhibitors could help treat prostate cancer. Presenilin 1 (PSEN1; PS1) is the catalytic subunit of g-secretase. In a human prostate cancer cell line, siRNA knockdown of PS1 decreased production of the intracellular domain (ICD) of transforming growth factor-b receptor 1 (TGFBR1; ALK5) compared with no alteration. In various human cancer cell lines and in a mouse xenograft model of prostate cancer, a g-secretase inhibitor decreased ICD formation, expression of proinvasive genes, the number of invasive cells and tumor volume compared with vehicle. Next steps include testing g-secretase inhibitors in in vivo models of metastasis and measuring TGFBR1 ICD levels in samples from patients with prostate cancer.
At least 10 companies have g-secretase inhibitors in Phase II or earlier testing to treat Alzheimer's disease (AD) or cancer.

SciBX 7(5); doi:10.1038/scibx.2014.142
Published online Feb. 6, 2014

Patented; available for licensing from the Ludwig Institute for Cancer Research Ltd.

Gudey, S.K. et al. Sci. Signal.; published online Jan. 7, 2014;
Contact: Marene Landström, Umeå University, Umeå, Sweden