Researchers Identify New Therapeutic Target for Prostate Cancer Treatment Resistance

Prostate cancer cells with a deletion of the SUCLA2 gene are linked to treatment resistance and metastasis but can be therapeutically targeted with the compound thymoquinone (TQ), according to a study published in Oncogene.

Hormone therapy is a standard treatment for metastatic prostate cancer. Almost half of patients develop resistance to this treatment after two years. Previous studies suggest that a mutation in tumor suppressor gene RB1 is a strong driver of treatment resistance and predicts prognosis in patients.

Researchers at Kanazawa University in Japan conducted an analysis of prostate cancer cells and found that cells with a RB1 deletion were also missing SUCLA2, a neighboring gene. After examining prostate cancer tissue, the team found that 11% of cases of advanced disease showed both RB1 and SUCLA2 deletion. Upon further analysis, they discovered that the frequency of SUCLA2 loss significantly aligned with RB1 loss at every disease stage, meaning that SUCLA2 deletion may be an identifier of patients who require advanced therapy.

The team worked to identify drugs to selectively target SUCLA2-deficient cells. They determined that TQ, which has been shown to be safe in a phase I clinical trial, was effective for this purpose. TQ treatment was applied to mouse models of SUCLA2-deficient prostate cancer and was shown to selectively suppress tumor growth.

“These findings show that TQ treatment could be an effective therapy for treating prostate cancer cells that harbor SUCLA2 deficiency,” senior author Chiaki Takahashi, MD, PhD, said in press release.