PSMA: A New Target for Prostate Cancer Treatment

Prostate cancer cells, colored red in scanning electron micrograph (SEM).
Summary

Prostate cancer cells have high levels of prostate-specific membrane antigen (PSMA), but researchers were unsure of its biological role. Now an MSK-led team has discovered that PSMA contributes to prostate cancer’s development. This offers a new target for drugs.

Highlights
  • PSMA is a protein in prostate cells.
  • Researchers have found that it helps fuel prostate cancer.
  • This offers a new target for prostate cancer treatments.

Prostate-specific antigen (PSA) can be an indicator of prostate cancer and is easily detected and measured with a blood test. But another protein, prostate-specific membrane antigen (PSMA), is also linked to prostate cancer. PSMA is present at a low level even in normal prostate tissue, but the amount is markedly higher in prostate cancer cells.

PSMA is a transmembrane protein — meaning it exists across the cell membrane — but 95 percent rests on the surface of prostate cells. Due to this external location, it is very accessible to researchers targeting it with molecules for the purpose of imaging or delivering drugs. Researchers have long regarded PSMA mainly as a means to an end, without fully understanding its biological purpose.

How PSMA Fuels Prostate Cancer

Now a team of researchers led by MSK radiologist and molecular imaging specialist Jan Grimm has discovered that PSMA plays a role in prostate cancer’s development. They report in the Journal of Experimental Medicine that PSMA indirectly activates a cancer-causing pathway that involves the PI3K protein kinase.

“Everybody knew that PSMA was related to more-aggressive prostate cancer, but nobody was able to figure out its biological role,” Dr. Grimm says. “Knowing how it helps trigger PI3K has important implications for treating men with prostate cancer.”

Everybody knew that PSMA was related to more-aggressive prostate cancer, but nobody was able to figure out its biological role.
Jan Grimm
Jan Grimm radiologist

In cell and animal experiments, as well as in tumor samples from patients, Dr. Grimm’s team found that PSMA causes the release of the amino acid glutamate, which acts as a second messenger to bind to a receptor on the surface of prostate cells. This binding transmits a signal to the cell to help activate the PI3K pathway. Dr. Grimm’s team showed that targeting PSMA with drugs slowed PI3K signaling, as well as the growth and spread of PSMA-expressing tumors, and, in the animal subjects, allowed them to live longer.

Dr. Grimm explains that PSMA inhibitors could potentially be used in combination with the existing prostate cancer drugs called androgen inhibitors, which block hormones that fuel cancer growth.

Some nutrients, such as vitamin B9, actually contain glutamate. This suggests that vitamin B9 could possibly play a small role in fueling prostate cancer through its interaction with PSMA, although Dr. Grimm cautions that more research needs to be done.

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Improving Prostate Cancer Classification and Treatment

The finding could also help doctors more accurately predict how a prostate tumor might behave in certain people. PSMA is easily detectable on PET scans. Such images could allow researchers to reliably detect the presence of cancer and to understand the cancer’s aggressiveness.

“This could help with prognoses and help doctors make better treatment decisions,” Dr. Grimm says. “For example, there are some men with aggressive prostate cancer that doesn’t have much PSMA expression, which may not need to be treated that aggressively.”

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The Role of PSMA in Solid Tumors

The role of PSMA in tumor growth is probably not limited to just prostate cancer, says Dr. Grimm. The protein is commonly found in the inner lining of blood vessels that supply other solid tumors, such as bladder cancer or colorectal cancer. Targeting PSMA in these blood vessels cells could starve a tumor to death by cutting off its food supply.

“We’re trying to apply what we’ve learned from the prostate cancer cells to see if the same effects hold true in these other settings,” Dr. Grimm says.

Dana Rathkopf
Prostate Cancer Treatments
We work with you to determine the best treatment for your prostate cancer — whether it’s surveillance, surgery, or other therapies. Learn more about our personalized approach.
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Comments

My body has been fighting MALIGNANT NEOPLASM prostate cancer as of 2015… PSA is now ~9. I run 1/2to1 hr/day. My 3/2/18 CT&Bscan clean. MY physical age: 82. Volunteer incite and NMNH in DC. Looking for help and support. (The oncologist suggests local PI trial in his hospital.)
What i need is summary of promising trials for my condition. Can you help?

Dear Kenneth, we recommend that you go to www.clinicaltrials.gov and search for trials that match up to your stage of disease and treatment history. If you'd like to have a consultation with an expert at MSK, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment.

Thank you for your comment and best wishes to you.

I would like to know if Sloan Kettering offers C-11 pet scans to locate reoccurring prostate cancer after a prostectomy . My PSA is rising at a fairly fast rate and would like information on getting the scan.

Dear William, MSK does offer C-11 PET scans in this circumstance. If you make an appointment with one our prostate cancer medical oncologists for a consultation, and if it appears that a C-11 choline scan is appropriate, then they will order it, review the result with you, and offer appropriate treatment options based on the result. The number to call for an appointment is 800-525-2225 and you can go to https://www.mskcc.org/experience/become-patient/appointment for more information. Thank you for your comment, and best wishes to you.

Research re PSMA radiotherapy for CRMPC in Australia. Is it offered here in USA yet.

I live in NYC, I recently had a radical prostectomy.
My PSA 4 weeks later 5.1
6 weeks later 4.8
8 weeks later 4.6
It would seem i still have cancer.
Is PSMA Pet scan available in NYC?

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