Hormone refractory prostate cancers more likely to spread to other organs

Prostate cancers that are resistant to androgen deprivation therapy are more invasive and more likely to spread to other organs than androgen dependent prostate cancers, UCLA cancer researchers have found.

Virtually all prostate cancers are androgen dependent at first, but they progress and become resistant over time. These hormone refractory or castration resistant cancers can grow despite surgical or medical therapies that deplete testosterone. The UCLA study is the first to link that progression with the cancer’s tendency to spread to other organs. The findings could change the way some prostate cancers are treated, spurring earlier use of hormone therapy to prevent the cancer’s spread, said Dr. Robert Reiter, a professor of urology, a researcher at UCLA’s Jonsson Cancer Center and senior author of the study.

Published in the Feb. 15 issue of the journal Cancer Research, the study makes the connection between androgen receptor and the spread of prostate cancer as well as the progression to androgen independence. Previous studies have shown that the androgen receptor is responsible for the growth of hormone refractory prostate cancer. However, no one has associated the spread of prostate cancer to the androgen receptor, Reiter said.

“We started noticing that the castration resistant prostate cancer models in the lab seemed to express genes that are typically associated with the spread of cancer,” Reiter said. “We began to ask what cell signaling pathways might be responsible. We looked at the androgen receptor and were surprised to find that it was not only overexpressed in castration resistant cancers but also in invasive cancers that still relied on androgen to grow.”

The study found that overexpression of the androgen receptor was critical to the cancer becoming more invasive. If a therapy could be found that blocked overexpression of the receptor, it might prevent the spread of certain prostate cancers.

Traditionally, doctors don’t like to use hormone treatment – which stops the production of testosterone - early on in the treatment of prostate cancer because of the harsh side effects, which can include hot flashes, osteoporosis and sexual dysfunction. In the past, doctors have waited until the cancer spread to prescribe hormone therapy, Reiter said.

“This study may provide additional scientific rationale to support the recent trend that giving hormone treatment early on is better than waiting,” Reiter said. “Early hormone treatment in this group of men might allow them to live longer. High levels of androgen receptor in the primary tumor might also predict which cancers are more likely to spread despite initial surgery or radiation.”

This strategy could be particularly effective in high risk men, those with large primary tumors, high Gleason scores and those that have lymph node involvement at diagnosis.

Prostate cancer is the most common cancer in men in the United States. This year alone, more than 218,000 men will be diagnosed with prostate cancer. About 27,000 men will die from the disease.

Reiter and his team will next seek to understand the mechanism by which androgen receptor overexpression is causing the cancer to spread. If they can uncover the mechanism, they might find new and better targets for drug therapy in addition to targeting the androgen receptor.

Source: University of California - Los Angeles

Related stories:

Androgen deprivation therapy for localized prostate cancer not associated with improved survival
A therapy that involves depriving the prostate gland the male hormone androgen is not associated with improved survival for elderly men with localized prostate cancer, compared to conservative management of the disease, according to a study in the July 9 issue of JAMA.
How advanced prostate cancer becomes resistant to androgen-deprivation therapy
For the past 70 years the treatment of choice for advanced, metastatic prostate cancer has been androgen-deprivation therapy. That is, the suppression of circulating testosterone – the hormone that fuels prostate-cancer growth – via surgical castration (orchiectomy) or medical castration with testosterone-blocking drugs. While such therapy buys time for patients, it is not a cure, as inevitably the cancer becomes resistant to the androgen deprivation and continues to grow.
Estrogen helps drive distinct, aggressive form of prostate cancer
Using a breakthrough technology, researchers led by a Weill Cornell Medical College scientist have pinpointed the hormone estrogen as a key player in about half of all prostate cancers.
Active surveillance a viable option for low-risk prostate cancer
Active surveillance remains a viable option for low-risk, localized prostate cancer, according to two studies presented today during the Annual Scientific Meeting of the American Urological Association (AUA), yet researchers point out a strong need for regular monitoring and development of stronger clinical predictors of progression.
Study shows that prostate cancer increases the risk of bone fracture
As unlikely as it sounds, scientists at the Garvan Institute for Medical Research have shown that there is a link between prostate cancer and a higher risk of bone fracture.
Study reveals inaccuracies in studies of cancer treatment
Certain biases may exist in observational studies that compare outcomes of different cancer therapies, making the results questionable. That is the conclusion of a new study published in the June 1, 2008 issue of CANCER, a peer-reviewed journal of the American Cancer Society. The research suggests that observational studies should include more thorough information and should be better designed to minimize inaccuracies.
Celebrex-Lipitor combo may halt prostate cancer
Researchers at Rutgers’ Ernest Mario School of Pharmacy have shown that administering a combination of the widely used drugs Celebrex (celecoxib, a nonsteroidal anti-inflammatory drug) and Lipitor (atorvastatin, a cholesterol lowering drug) stops the transition of early prostate cancer to its more aggressive and potentially fatal stage.
Blocking protein kills prostate cancer cells, inhibits tumor growth
Researchers at Jefferson’s Kimmel Cancer Center in Philadelphia have shown that they can effectively kill prostate cancer cells in both the laboratory and in experimental animal models by blocking a signaling protein that is key to the cancer’s growth. The work proves that the protein, Stat5, is both vital to prostate cancer cell maintenance and that it is a viable target for drug therapy.

News discussion:

Medicine & Health news