Three-Gene Blood Test May Predict Resistance to Hormonal Therapy in Metastatic Prostate Cancer

A new study published in Frontiers in Oncology suggests that a simple blood test measuring the activity of three genes could help predict which men with metastatic hormone-sensitive prostate cancer (mHSPC) are more likely to develop resistance to hormonal treatment.

Researchers followed 157 men with newly diagnosed metastatic prostate cancer who were receiving androgen deprivation therapy (ADT) combined with an androgen receptor pathway inhibitor, sometimes alongside docetaxel. Of these, 147 completed follow-up. By analyzing gene activity in blood samples, the researchers developed a prediction model based on three genes: SLC25A39, SLC6A8, and YBX3.

The test showed encouraging accuracy in identifying patients at greater risk of progressing to metastatic castration-resistant prostate cancer (mCRPC). Its predictive performance, measured by the area under the curve (AUC), reached 0.89 in the development group and 0.83 in the validation group. Patients classified as high risk were considerably more likely to develop resistance, with a reported hazard ratio of 17.19. Their median time before castration-resistant progression was approximately 15.5 months, while it had not yet been reached in the low-risk group.

One of the three genes, SLC6A8, may also play a direct role in cancer progression. It is involved in transporting creatine into cells, helping support their energy metabolism. In laboratory experiments, blocking SLC6A8 reduced prostate cancer cell growth and activity in metabolic pathways involved in energy production.

These findings are interesting for two reasons. First, a blood-based test could eventually help doctors identify patients who need closer monitoring. Second, SLC6A8 itself could become a potential therapeutic target, linking cancer progression to the way tumor cells obtain and use energy.

The main limitation is that the model has not yet been validated in a completely independent patient population. The study was relatively small, and the large estimated difference between risk groups came with considerable statistical uncertainty. As usual, larger studies will be needed to determine whether the test can reliably improve treatment decisions.

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