Boyang (Jason) Wu, an associate professor in the WSU College of Pharmacy and Pharmaceutical Sciences and co-senior author on the study. Credit: WSU
Key points:
- Researchers have identified a receptor protein called CHRM1 that underlies prostate cancer cells’ resistance to docetaxel—a chemotherapy drug used to treat advanced cancer that has spread beyond the prostate.
- Researchers used dicyclomine to block CHRM1 in resistant prostate cancer cells and restore docetaxel’s ability to kill cancer cells and stop tumor growth.
- Combining dicyclomine and docetaxel made treatment more effective and this type of combination therapy may be used for other cancers treated with docetaxel, such as breast and lung cancer.
Researchers have identified a receptor protein called CHRM1 that underlies prostate cancer cells’ resistance to docetaxel—a chemotherapy drug used to treat advanced cancer that has spread beyond the prostate. This discovery, published in Cell Reports Medicine, uncovers new treatment strategies that may extend the lives of those with prostate and other cancers.
Researchers used dicyclomine—a drug used to treat irritable bowel syndrome that selectively inhibits CHRM1 activity—to block CHRM1 in both resistant prostate cancer cell lines and animal models based on patient-derived resistant tissue. They found that dicyclomine restored docetaxel’s ability to kill cancer cells and stop tumor growth.
Docetaxel resistance can develop as soon as six months into treatment, which is a major obstacle for patients with castration-resistant prostate cancer who rely on chemotherapy drugs like docetaxel when hormone therapy fails. Importantly, the current study supports the need for clinical testing to determine if combined use of docetaxel and dicyclomine help overcome treatment resistance in prostate cancer patients.
The research team also found that blocking CHRM1 in cancer cells made docetaxel more efficient. Prostate cancer patients may benefit from a combination treatment strategy even before docetaxel resistance develops.
“What this suggests is that the lowest effective dose of docetaxel may be lower when the drug is combined with dicyclomine, compared to when docetaxel is used alone,” said study author Boyang (Jason) Wu, professor at Washington State University. “Being able to use a lower dose could help reduce unwanted side effects and make treatment more manageable for patients.”
The team hopes to continue their research to determine if combination therapy could be used for other cancers treated with docetaxel, such as breast and lung cancer. They also want to explore if the combination strategy could apply to other similar chemotherapy drugs.