Prostate cancer is one of the leading causes of cancer deaths among men worldwide. It can be treated with hormone therapy, surgery, radiation, or chemotherapy, depending on the stage and aggressiveness of the disease. However, some patients develop resistance to these treatments, especially to docetaxel, a widely used chemotherapy drug for advanced prostate cancer that has spread beyond the prostate.
Docetaxel works by interfering with the division of cancer cells, causing them to die. However, over time, some cancer cells can adapt and survive the drug’s effects, making it less effective and limiting the patient’s options and prognosis.
Researchers from Washington State University have identified a receptor protein called CHRM1 as a key factor in prostate cancer cells’ resistance to docetaxel. CHRM1 is normally involved in regulating muscle contraction and relaxation, but it also plays a role in cell survival and proliferation.
The researchers found that CHRM1 is overexpressed in docetaxel-resistant prostate cancer cells and tissues, compared to sensitive ones. They also showed that blocking CHRM1 with a drug called dicyclomine restored docetaxel’s ability to kill resistant cells and stop tumor growth in cell lines and an animal model based on patient-derived resistant tissue.
Dicyclomine is already approved as a generic drug to treat symptoms of irritable bowel syndrome. It selectively inhibits CHRM1 activity without affecting other receptors or causing major side effects.
The researchers suggest that combining docetaxel with dicyclomine could help overcome treatment resistance in prostate cancer patients and perhaps other cancers that are treated with docetaxel, such as breast and lung cancer. This could improve the efficacy and duration of chemotherapy and extend the lives of patients.
The study was published in the journal Cell Reports Medicine on January 22, 2024. The researchers plan to conduct clinical trials to test the safety and effectiveness of this combination therapy in prostate cancer patients.