Research helps explain why androgen-deprivation therapy doesn't work for many prostate cancers

January 5, 2017
Micrograph showing prostatic acinar adenocarcinoma (the most common form of prostate cancer) Credit: Wikipedia

Metastatic prostate cancer, or prostate cancer that has spread to other organs, is incurable. In new research published in the journal Science, Roswell Park Cancer Institute scientists have identified two gatekeeper genes that allow prostate cancer to progress and resist treatment. Their work illuminates the mechanisms behind lineage plasticity, the ability of prostate cancer to adapt to therapy, and highlights opportunities to disrupt and even reverse this deadly process.

"Androgen-deprivation therapy is commonly used to treat patients whose prostate cancer has spread beyond the prostate. While most men initially respond to this therapy, the cancer nearly always returns and is often aggressive and lethal. We have discovered a mechanism that causes progression to this aggressive form of prostate cancer, providing a new opportunity to prevent or treat lethal forms of prostate cancer," says co-senior author David Goodrich, PhD, Professor of Oncology in the Department of Pharmacology and Therapeutics at Roswell Park.

"Importantly, these findings offer a new understanding of prostate cancer lineage plasticity, which involves the conversion of cancer cells that are dependent on a specific therapeutic target to that are now indifferent to that target's function," adds co-senior author Leigh Ellis, PhD, Assistant Professor of Oncology in the Department of Pharmacology and Therapeutics. "This discovery offers the possibility to reverse or delay lineage plasticity, thereby prolonging the effectiveness of the currently used therapies, like androgen deprivation. And this new understanding has the potential to be applicable in other types of cancers."

Using preclinical models, the scientists demonstrated that loss of the tumor-suppressor gene known as Rb1 induces lineage plasticity and metastatic progression of prostate cancer. They also show that increased expression of another gene, Ezh2, is associated with lineage plasticity and may be therapeutically exploited. Treatment of resistant tumors with drugs that inhibit the Ezh2 gene may resensitize to androgen-deprivation therapy. The team expects to pursue these findings further in clinical studies at Roswell Park.

Explore further: New findings concerning hereditary prostate cancer

More information: "Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance," Science, science.sciencemag.org/cgi/doi … 1126/science.aah4199

Related Stories

New findings concerning hereditary prostate cancer

July 11, 2016
It is a well-known fact that men with a family history of prostate cancer run an increased risk of developing the disease. The risk for brothers of men with prostate cancer is doubled. But a doubled risk of what, exactly? ...

New genetic discovery advances understanding of prostate cancer

October 26, 2015
A new and important genetic discovery, which sheds light on how prostate cancers develop and spread, has been made by an international research team led by scientists at The University of Nottingham.

A new method for prostate cancer imaging

July 21, 2016
Prostate cancer is one of the most common cancers in men. Tumor growth is critically regulated by the androgen receptor, and treatment strategies to lower androgens, such as testosterone, are a mainstay of clinical treatment. ...

Compound shows promise as next-generation prostate cancer therapy

August 8, 2016
In the search for new ways to attack recurrent prostate cancer, researchers at Duke Health report that a novel compound appears to have a unique way of blocking testosterone from fueling the tumors in mice.

Prostate cancer discovery may make it easier to kill cancer cells

December 18, 2015
A newly discovered connection between two common prostate cancer treatments may soon make prostate cancer cells easier to destroy. Drugs that could capitalize on the discovery are already in the pipeline, and a clinical trial ...

Cancer researchers identify new metastasis suppressor gene

July 14, 2014
(Medical Xpress)—Among patients with deadly cancers, more than 90 percent die because of metastatic spread of their disease. Looking to target a key pathway in order to interfere with the processes that lead to tumor spread, ...

Recommended for you

Encouraging oxygen's assault on iron may offer new way to kill lung cancer cells

November 22, 2017
Blocking the action of a key protein frees oxygen to damage iron-dependent proteins in lung and breast cancer cells, slowing their growth and making them easier to kill. This is the implication of a study led by researchers ...

One in four U.S. seniors with cancer has had it before

November 22, 2017
(HealthDay)—For a quarter of American seniors, a cancer diagnosis signals the return of an old foe, new research shows.

Combination immunotherapy targets cancer resistance

November 22, 2017
Cancer immunotherapy drugs have had notable but limited success because in many cases, tumors develop resistance to treatment. But researchers at Yale and Stanford have identified an experimental antibody that overcomes this ...

Researchers discover specific tumor environment that triggers cells to metastasize

November 21, 2017
A team of bioengineers and bioinformaticians at the University of California San Diego have discovered how the environment surrounding a tumor can trigger metastatic behavior in cancer cells. Specifically, when tumor cells ...

New study points the way to therapy for rare cancer that targets the young

November 21, 2017
After years of rigorous research, a team of scientists has identified the genetic engine that drives a rare form of liver cancer. The findings offer prime targets for drugs to treat the usually lethal disease, fibrolamellar ...

Clinical trial suggests new cell therapy for relapsed leukemia patients

November 20, 2017
A significant proportion of children and young adults with treatment-resistant B-cell leukemia who participated in a small study achieved remission with the help of a new form of gene therapy, according to researchers at ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Dug
not rated yet Jan 06, 2017
Why not look more at the genes that change in the metabolism of 20-40 year old males, compared to 40-70 year old males. Prostate cancer is just one more of the many genetic default program of aging diseases (diseases primarily associated with aging). Let's look harder at stabilizing the genetic program of healthy youth rather than to trying to treat all the disease create by genes telling the body to essentially shut down and die. Yes, I know that farming the aging is the business model of big pharma, but that has to change because we simply can't afford to do otherwise. The implications of the lack of ethical and moral direction of big pharma's avoidance of cures and focus on treating diseases are extraordinarily negative.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.