Can Siah2 predict aggressive neuroendocrine prostate cancer?

It has been known for years that some types of prostate cancer are more aggressive than others, and that among those more aggressive types are prostate cancer tumors that include so-called “neuroendocrine” cell types. The ability to easily identify neuroendrocrine prostate cancer cells at biopsy would improve the quality of diagnosis and potentially affect the ways in which patients with such a diagnosis could be treated.

A recent article by Qi et al. has described the identification of a series of proteins that seem to affect the likelihood of the development and metastasis of neuroendocrine prostate cancer cells. In particular, the authors describe a protein named Siah2, which can initiate a sequence of molecular events that turns a non-malignant tumor into a metastatic neuroendocrine tumor. Additional information is available in a media release from the Sanford-Burnham Medical Research Institute.

Neuroendocrine cells can be found in about 30 percent of all adenocarcinomas of the prostate. On a much rarer basis, some aggressive prostate tumors appear to be made up entirely of neuroendocrine-type cells. Qi et al. were able to use human prostate cancer samples to show that Siah2 and the other proteins it triggers are detected much more often in the aggressive neuroendocrine forms of prostate tumors than in other types.

In preliminary laboratory research Qi et al. were also able to inactivate the gene for Siah2 expression in a mouse-based model of aggressive prostate cancer. They found that in these mice — although benign (non-cancerous) growths still appeared — there was no evidence of the development of neuroendocrine tumors.

The implication here is that it may it be possible to make better diagnostic and prognostic decisions through the identification of the presence of the Siah2 protein in a patient’s prostate tissues and it may be possible to identify or develop molecules that can inhibit the activity of Siah2 and/or other proteins in the downstream sequence that trigger and stimulate metastasis. However, there is a lot more work that would be needed to bring these possibilities into the clinic.

One Response

  1. Maybe and might — mice and petri dishes — not much different to the broccoli story.

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