Nav: Home

Researchers identify new therapeutic target for metastatic prostate cancer

May 15, 2019

Researchers in New York have found that treating human prostate cancer cells with a drug that targets a protein called PHLPP2 may prevent the cancer cells from spreading to other organs in the body. The study, which will be published May 15 in the Journal of Cell Biology, reveals that inhibiting PHLPP2 lowered the levels of MYC, an oncogenic protein that causes many different types of cancer that cannot be targeted by conventional drug therapies.

MYC is a powerful oncogene because it drives cell growth and proliferation and enhances cell metabolism and survival. "It is estimated that 450,000 Americans are diagnosed each year with a cancer that is driven by MYC," says co-senior author Dawid G. Nowak, who is currently an assistant professor at Weill Cornell Medicine.

One type of cancer associated with elevated MYC levels is metastatic prostate cancer. According to the American Cancer Society, around one in nine men will be diagnosed with prostate cancer during their lifetime. The disease is the second leading cause of cancer death among American men and is projected to kill over 30,000 people in 2019. The vast majority of these deaths are the result of cancers that spread, or metastasize, from the prostate to other organs in the body.

"The five-year survival of metastatic prostate cancer is only 28%, whereas the five-year survival of prostate-confined disease is almost 99%," explains Lloyd C. Trotman, a professor at Cold Spring Harbor Laboratory and co-senior author of the new study.

The protein PHLPP2 is also elevated in metastatic prostate cancer cells. PHLPP2 is a phosphatase enzyme that can remove phosphate groups from other proteins, but the role of this protein in prostate cancer was previously unclear. In the new study, Nowak, Trotman, and colleagues found that metastatic prostate cancer cells require PHLPP2 to survive and proliferate. They discovered that PHLPP2 helps stabilize MYC by removing a phosphate group that would otherwise trigger MYC's destruction.

The researchers deleted the Phlpp2 gene in mice and found that doing so prevented prostate cancer cells from metastasizing to other organs. This is significant because researchers have been unable to develop treatments that directly inhibit MYC, as it does not contain any features that can be easily targeted with a drug.

Trotman and colleagues then turned to human prostate cancer cells, which they treated with a drug that inhibits PHLPP2. This lowered MYC levels and caused the cells to stop proliferating and die.

PHLPP2 does not appear to perform any essential functions in healthy cells, so researchers suggest the enzyme could be an attractive way to indirectly target MYC in metastatic prostate cancer and possibly other cancers, too.

"Our results suggest that targeted efforts to design pharmacologically relevant PHLPP2 inhibitors could result in very efficient new drugs that suppress MYC-driven cancer," Trotman says.
-end-
Nowak et al., 2019. J. Cell Biol.http://jcb.rupress.org/cgi/doi/10.1083/jcb.201902048?PR

About the Journal of Cell Biology

TheJournal of Cell Biology (JCB)features peer-reviewed research on all aspects of cellular structure and function. All editorial decisions are made by research-active scientists in conjunction with in-house scientific editors. JCBmakes all of its content free online no later than six months after publication. Established in 1955, JCB is published by the Rockefeller University Press. For more information, visit jcb.org.

Visit our Newsroom, and sign up for a weekly preview of articles to be published. Embargoed media alerts are for journalists only.

Follow JCB on Twitter at @JCellBiol and @RockUPress.

Rockefeller University Press

Related Prostate Cancer Articles:

ASCO and Cancer Care Ontario update guideline on radiation therapy for prostate cancer
The American Society of Clinical Oncology (ASCO) and Cancer Care Ontario today issued a joint clinical practice guideline update on brachytherapy (internal radiation) for patients with prostate cancer.
Patient prostate tissue used to create unique model of prostate cancer biology
For the first time, researchers have been able to grow, in a lab, both normal and primary cancerous prostate cells from a patient, and then implant a million of the cancer cells into a mouse to track how the tumor progresses.
Moffitt Cancer Center awarded $3.2 million grant to study bone metastasis in prostate cancer
Moffitt researchers David Basanta, Ph.D., and Conor Lynch, Ph.D., have been awarded a U01 grant to investigate prostate cancer metastasis.
New findings concerning hereditary prostate cancer
For the first time ever, researchers have differentiated the risks of developing indolent or aggressive prostate cancer in men with a family history of the disease.
Prostate cancer discovery may make it easier to kill cancer cells
A newly discovered connection between two common prostate cancer treatments may soon make prostate cancer cells easier to destroy.
New test for prostate cancer significantly improves prostate cancer screening
A study from Karolinska Institutet in Sweden shows that a new test for prostate cancer is better at detecting aggressive cancer than PSA.
The dilemma of screening for prostate cancer
Primary care providers are put in a difficult position when screening their male patients for prostate cancer -- some guidelines suggest that testing the general population lacks evidence whereas others state that it is appropriate in certain patients.
Risk factors for prostate cancer
New research suggests that age, race and family history are the biggest risk factors for a man to develop prostate cancer, although high blood pressure, high cholesterol, vitamin D deficiency, inflammation of prostate, and vasectomy also add to the risk.
Prostate cancer is 5 different diseases
Cancer Research UK scientists have for the first time identified that there are five distinct types of prostate cancer and found a way to distinguish between them, according to a landmark study published today in EBioMedicine.
UH Seidman Cancer Center performs first-ever prostate cancer treatment
The radiation oncology team at UH Seidman Cancer Center in Cleveland performed the first-ever prostate cancer treatment April 3 using a newly-approved device -- SpaceOAR which enhances the efficacy of radiation treatment by protecting organs surrounding the prostate.

Related Prostate Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Jumpstarting Creativity
Our greatest breakthroughs and triumphs have one thing in common: creativity. But how do you ignite it? And how do you rekindle it? This hour, TED speakers explore ideas on jumpstarting creativity. Guests include economist Tim Harford, producer Helen Marriage, artificial intelligence researcher Steve Engels, and behavioral scientist Marily Oppezzo.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".