Advancements in treating chemotherapy-resistant prostate cancer

The researchers verified that human prostate cancer cells thrive using fatty acid oxidation by assessing the biopsies of 38 people with the disease. The cisplatin prodrug Platin-L, which has a cisplatin molecule bound to a 12-carbon fatty acid on one side and succinate on the other side, had the greatest effect by binding to a key protein required for long-chain fatty acid transport, a primary step in this metabolic process. And in trials, Platin-L reduced the growth of prostate cancer cells by over 50% in several different cell lines.

To develop a treatment that could be taken orally, the researchers encapsulated Platin-L in nanoparticles made with a biocompatible polymer that targeted prostate cancer cells. They administered the nanoparticles to mouse models with cisplatin-resistant prostate cancer and observed that the tumors shrunk, whereas tumors in animals treated with saline or cisplatin grew. Additionally, the Platin-L nanoparticle-treated mice had steady body weight, increased survival rates, and didn’t display peripheral neuropathy.

Reference: New Pathway for Cisplatin Prodrug to Utilize Metabolic Substrate Preference to Overcome Cancer Intrinsic Resistance, ACS Central Science, DOI 10.1021/acscentsci.3c00286