Protein discovery could help solve prostate cancer drug resistance (“Dramatic” effect from $10 a month drug (dicyclomine))

Medical Xpress / Washington State University / Cell Reports Medicine ^ | Jan. 22, 2024 | Boyang (Jason) Wu et al

[ConservativeMind]

Researchers have identified a receptor protein known as CHRM1 as a key player in prostate cancer cells' resistance to docetaxel, a commonly-used chemotherapy drug to treat advanced cancer that has spread beyond the prostate.

The discovery opens the door to new treatment strategies that could overcome this resistance.

The study showed that blocking CHRM1 in resistant prostate cancer cell lines and an animal model based on patient-derived resistant tissue restored docetaxel's ability to kill cells and stop tumor growth. The researchers did this by using dicyclomine, a drug that selectively inhibits CHRM1 activity. Dicyclomine is already on the market as a generic drug and is currently used to treat symptoms of irritable bowel syndrome.

"The effect was pretty dramatic in all the experimental models we tested," said Boyang (Jason) Wu.

Docetaxel resistance can develop in prostate cancer after about six months of treatment. Chemotherapy drugs like docetaxel are among very few options available to patients with castration-resistant prostate cancer, a lethal form of the disease that no longer responds to hormone therapy.

Wu said this type of combination therapy could also potentially be used for other cancers treated with docetaxel, such as breast and lung cancer. It may also be possible to use the same combination strategy with other similar chemotherapy drugs.

In addition to testing resistant cancer cell lines, the research team also tested cells that still responded to docetaxel treatment. They found that using dicyclomine to block CHRM1 in these cells made docetaxel more efficient at killing them. Wu said that prostate cancer patients could potentially 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," Wu said.

[ConservativeMind]

Castration-resistant prostate cancer treatment (and possibly that of other cancers) can be greatly enhanced and made effective again through docetaxel, with a $10 drug, dicyclomine.

[ConservativeMind]

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