New genetic mechanism explains prostate cancer progression in androgen-suppressed patients

According to a media release from Cancer Research UK yesterday, “The first-ever comprehensive study of prostate cancer tissue has revealed a completely new gene network driving the disease in patients who have stopped responding to standard hormone treatment.”

The media release is based on a paper by Sharma et al. just published on line in Cancer Cell. The full text of the media release is available on line.

The basic finding of the new study by Sharma and her colleagues is that when the presence of androgens in the bloodstream is suppressed (using any of a variety of androgen deprivation therapies), androgen receptors continue to fuel the spread of prostate cancer by switching on a completely different set of 16 genes, including genes associated with the production of glucose and fats.

The fact that prostate cancer can be spread through the action of more than one set of genetic drivers is not exactly a shocking finding. We know that men on primary androgen deprivation therapy (ADT) become castration-resistant over time, which has long implied the induction of a different mechanism for the continued spread of cancer in castration-reistant patients. The interesting question will be whether this finding of the involvement of a specific genetic mechanism explaining the induction of progression in men when they become castrate resistant can help us to develop better forms of therapy for such patients.

According to Dr. Sharma, quoted in the media release, the team’s findings do indeed help to “provide fresh targets for the development of new drugs to treat advanced stages of prostate cancer, and new ‘flags’ to help doctors track the progression of the disease in patients.”

3 Responses

  1. Thanks for posting this, Sitemaster. I shall download the article soon. It is clearly important. I would like to know more about the continued, cancer-fuelling, function of androgen receptors after failure of ADT and in the absence of androgens.

  2. Dear George:

    There is an enormous literature on how androgen receptors are stimulated in castration-resistant patients. We have a pretty good idea what happens. To date, however, we have very little understanding of exactly why it happens (i.e., how the relevant pathways are “switched on”).

    Please understand that standard forms of androgen deprivation therapy do not remove all androgens from the body. They are designed to block the normal production of testosterone and its conversion to dihydrotestosterone. In men who become castration-resistant, the secondary (adrenal) androgen pathways are hijacked to induce the development of dihydrostestosterone by other means. The paper by Sharma et al. offers a possible explanation for what drives this effect.

    What we are dealing with here is a classic biochemical feedback loop system. Block the development of a biochemical essential to normal human function in one way, and the body responds by finding another way to make the essential biochemical.

  3. I know. I realised that shortly after I used the word “absence.” Still, I find it interesting, and hope to look at some of that literature. Whilst I probably know enough chemistry and cell biology, I lack the understanding of molecular genetics to understand this, right now. I can, though, probably pick up enough while reading about this.

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