• Posted July 13, 2023

New Type of Treatment Tackles Tough-to-Treat Prostate Cancer

A preclinical study offers a potential new therapy for treatment-resistant prostate cancer, offering new hope for men with the disease.

The study used the chemotherapy drug cisplatin, administered orally, to disrupt the metabolism of prostate cancer cells and bring the medication directly into treatment-resistant cells.

University of Miami researchers validated their targets in human prostate cancer biopsies. Then they tested the treatment in human cancer cells and a mouse model of prostate cancer, to show it could be safe and effective in shrinking these cancers.

Cisplatin is a potent drug but it has not been effective in treating prostate cancer.

For this study, the researchers used a compound called Platin-L to break down a process that malignant prostate cancer cells use to fuel their growth and also to deliver the cisplatin directly into treatment-resistant cancer cells.

"We believe Platin-L can circumvent these resistance mechanisms,"said senior study author Shanta Dhar, assistant director of technology and innovation at the university's Sylvester Comprehensive Cancer Center.

Prostate cancer differs from most other cancers. While most cancers use a biochemical reaction to turn glucose into energy to support their growth and spread, as prostate cancer advances, it instead alters enzymes that enable it to get energy from fat instead of sugar. That process is called fatty acid oxidation (FAO).

Platin-L targets CPT1A, a protein that is a part of this process.

"We are also making prostate cancer cells choose a less favorable metabolic pathway, which is insufficient to their needs, making it difficult for them to survive,"Dhar said.

The researchers treated patient prostate tumor samples as well as cisplatin-resistant animal models. Platin-L destroyed the cancer cells by robbing them of their energy source, dismantling both mitochondrial and nuclear DNA.

The medication is what's known as a "prodrug"because it only activates when the body metabolizes it, the study authors explained in a university news release.

For the study, Platin-L was encapsulated in nanoparticles targeting a protein called prostate-specific membrane antigen (PSMA). This made it possible to administer the drug orally.

Side effects in other parts of the body were limited. In the study's mouse models, tumors shrank and the treated mice had steady body weight, increased survival rates and little evidence of the peripheral nerve damage that often results from cisplatin treatment.

The researchers think other nanoparticles could be engineered to target other cancers.

"We made a dual-targeted nanoparticle,"Dhar said. "The first targeting is needed to get it through the gut barrier, and the second targeting takes it to the prostate. The beauty is, now we can deliver a cisplatin-based chemotherapeutic orally, which is usually never done. And by targeting the prostate, we can reduce kidney and liver toxicity and the risk of peripheral neuropathy."

The results appear promising for future clinical trials and development, Dhar said.

"The impact of this current targeted metabolic modulation of the tumor microenvironment for advanced prostate cancer extends beyond this cancer type,"the authors wrote. "The reported mechanistic investigations will allow us to find the clues to make this platform more general to be used for cancers where these cellular pathways can be altered."

The study was published July 12 in ACS Central Science, an American Chemical Society journal.

More information

The Urology Care Foundation has more on prostate cancer.