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The next generation of hormonal therapies for prostate cancer

Posted Apr 22 2010 12:00am

Beyond abiraterone acetate and MDV3100 and even TAK-700, a new generation of treatments for hormonally driven cancers like prostate cancer (and breast cancer) is being explored by start-up companies like Aragon Pharmaceuticals .

The standard therapies for prostate cancer drugs like leuprolide acetate and bicalutamide were designed to block processes leading to the conversion of androgens like testosterone into metabolites like  dihydrotestosterone that stimulated the cancer’s growth. In the words of Rich Heynman, PhD, the president of Aragon, they work like “glue in the lock” of hormone receptors, by temporarily gumming up the mechanism of androgen stimulation.

After a while, however, these drugs always stop working. Forms of prostate cancer cell that are resistant to these hormonal therapies start to become dominant; patients become treatment resistant (i.e., they develop hormone-refractory or castration-resistant prostate cancer); and in some cases the hormonal treatment that used to delay growth of hormone-sensitive prostate cancer cells actually starts to stimulate growth of the hormone-resistant cells.

Aragon is working on newer drugs that are designed to have very different mechanisms of action but still work within the hormonal cycle.  The company’s first drug, ARN-509, is expected to enter Phase I clinical trials later this year. It is designed to completely block activity of the androgen receptor when in hormone-resistant prostate cancer cells. Another Aragon program is based on agents (selective androgen receptor degraders) that will destroy the androgen receptor entirely, making it impossible for androgens to stimulate the growth of prostate cancer cells.

Obviously we will have to wait to see whether these new classes of drug have the clinical activity needed to become effective in the treatment of (at least initially) advanced forms of prostate cancer. And of course they will need to display that activity with limited adverse effects to get approval for widespread clinical use. However, we continue to see a great deal of innovation in the development of drug therapies specifically targeted to the hormonal feedback system that drives the development of prostate cancer. Perhaps the next generation of hormonal therapies for prostate cancer will be ready for testing in large-scale clinical trials some time in the next 3 years or so.

Aragon Pharmaceuticals is also working on comparable products (selective estrogen receptor degrading agents) that may have activity in the treatment of some types 0f breast cancer.

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