Research Finds 2 New Targets for Prostate Cancer Therapies

December 12, 2020
AJMC Staff

The genes are part of the family that cause cancer cells to grow.

Two genes that cause cancer cells to become resistant to treatment have been identified by a scientist at the University of Georgia, who reports that these genes could offer drug developers new therapeutic targets..

Findings published in journal Molecular Cancer Research report that ACSL3 and ACSL4 function in tandem, and their levels of expression rise and fall relative over the course of prostate cancer treatment. The journal is published by the American Association for Cancer Research.

The genes, which are part of the same family that propel cancer cell growth, are regulated in a complementary, “yin-yang” fashion, wrote the study authors, led by senior author Houjian Cai, associate professor in the university’s College of Pharmacy.

“In the early stage of cancer, ACSL3 is high and ACSL4 is low. With castration treatment, expression of the ACSL3 gene becomes low, but ACSL4 becomes high,” Cai said in a statement. “In order to treat the cancer cells effectively, you have to somehow simultaneously target the pathway driven by these two genes.”

However, as prostate cancer can become resistant to castration treatment, expression of the ACSL4 gene increases; as that occurs, expression of ACSL3 is lower.

Researchers established their findings by suppressing the ACSL4 gene and studying how the cancer cells responded; they then used a mouse model to inhibit ACSL4 expression to see if tumors in the mice would shrink. In each case, blocking the ACSL4 gene suppressed the cancer cells. “Identifying the ACSL4 gene as a target for castration treatment-resistant prostate cancer is the first step,” Cai said. “The next step is to find a drug that will inhibit the gene.”

The CDC reports that prostate cancer is the second leading cause of cancer deaths among men in the United States. Suppressing the male hormone that lets cancer grow, known as castration treatment, is the main weapon against prostate cancer.

Reference

Ma Y, Zhang X, Slsaidan OA, et al. Long-chain acyl-CoA synthetase 4–mediated fatty acid metabolism sustains androgen receptor pathway–independent prostate cancer. Mol Cancer Res. Published December 1, 2020. doi: 10.1158/1541-7786.MCR-20-0379