According to a new study published in Oncogene, the compound thymoquinone (TQ) specifically kills prostate cancer cells at advanced stages. Prostate cancer cells with a deletion of the SUCLA2 gene can be therapeutically targeted, according to a study led by Kanazawa University researchers.
Patients with SUCLA2-deficient prostate tumors are more likely to be resistant to hormone therapy or metastatic, therefore a novel therapeutic option for this condition would be extremely beneficial.
Hormone therapy is frequently used to treat metastatic prostate cancer, but nearly half of patients develop resistance to it after just two years.
A mutation in the tumor suppressor gene RB1, which regulates cell proliferation, has been identified as a particularly powerful cause of treatment resistance and predicts poor patient outcomes.
“Mutations in tumor suppressor genes are enough to induce initiation and malignant progression of prostate cancer, but so far we haven’t been able to directly target these mutations with drugs to treat prostate cancer,” says the lead author Susumu Kohno.
“We wanted to find a genetic aberration associated with that of a tumor suppressor gene which we could target therapeutically.”
Mutations in tumor suppressor genes are enough to induce initiation and malignant progression of prostate cancer, but so far we haven’t been able to directly target these mutations with drugs to treat prostate cancer. We wanted to find a genetic aberration associated with that of a tumor suppressor gene which we could target therapeutically.
Susumu Kohno
SUCLA2 shares a genome with RB1. A study of prostate cancer cells revealed that cells lacking RB1 also lacked SUCLA2, tying the SUCLA2 deletion to the RB1 loss found in advanced-stage prostate cancer. When Kohno and colleagues examined prostate cancer tissue, they discovered that 11% of tumors lacked both SUCLA2 and RB1.
The researchers looked for medicines that would selectively kill cells with a SUCLA2 deletion by screening chemicals. TQ was selected as a hit compound from a pool of over 2,000 compounds.
TQ has been demonstrated to have anti-cancer properties and to be safe in a phase I clinical investigation. TQ selectively inhibited tumor growth in a mouse model of SUCLA2-deficient prostate cancer, according to Kohno and colleagues.
“These findings show that TQ treatment could be an effective therapy for treating prostate cancer cells that harbor SUCLA2 deficiency,” says the senior author Chiaki Takahashi.
The researchers discovered that the frequency of SUCLA2 loss was almost precisely correlated with RB1 loss at every disease stage in a search of genetic databases from patients with prostate cancer, implying that SUCLA2 deletion could identify persons with prostate cancer who require advanced therapy.
The discovery of this drug-targetable weakness breaks through the treatment resistance barrier in prostate cancer. Although further research is needed to increase TQ’s efficacy and identify patients who would benefit from this form of treatment, the molecule appears to be a viable route to new treatment choices for advanced prostate cancer.
