Aurora A kinase inhibition and treatment of neuroendocrine prostate cancer

A research team in Los Angeles has demonstrated that a protein produced by a cancer gene (the MYCN gene) leads to the development of the often deadly, late-stage form of prostate cancer called neuroendocrine prostate cancer.

The paper describing this research, by Lee et al., was published recently in Cancer Cell, and readers can also get more information from this media release from the University of California, Los Angeles.

Lee et al. have shown that:

  • N-Myc and AKT1 drive development of neuroendocrine prostate cancer from human prostate epithelium.
  • Prostate epithelial cells can give rise to neuroendocrine and epithelial cancers.
  • N-Myc is essential for tumor maintenance in tumors initiated by N-Myc and AKT1.
  • Destabilization of N-Myc through inhibition of the enzyme aurora A kinase can induce tumor cell death.

They also showed that an experimental drug called CD532, which acts on aurora A kinase, could reduce the size of neuroendocrine prostate cancer tumors that had been implanted in mice by 80 percent.

Dr. Lee is quoted as saying that the research team’s next steps will be to try and identify drugs other than CD532 that may be effective for treating neuroendocrine prostate cancer. This would seem to suggest that CD532 is not, in and of itself, a good candidate for use as a drug in humans. To date, CD532 has only been used in preclinical studies, has not been tested in humans at all, and quite certainly has not been approved by the U.S. Food and Drug Administration as safe and effective for use in humans (for any type of cancer treatment).

One Response

  1. Neuroendocrine cancer is not necessarily late stage. My understanding is that it is diagnosed in 1%-2% of all men and can be found at an early stage. It is, however, a different cancer type and one that to date has been hard to manage.

    What can be late stage is a morphed cancer like IAC (intermediate atypical carcinoma found last year by the West Coast Dream Team) that develops in late stage and has many features of neuroendocrine/small cell disease.

    The mis-characterization lies with the UCLA PR folks who have incorrectly described the finding. What the summary of the paper actually says is:
    “We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease.”

    My educated guess is that these characteristics are found in the morphed disease too, and this may be a significant finding in how to treat it. Owen Witte is the joint Director of the West Coast Dream Team with Eric Small; this is coming directly out of that research.

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this: