Researchers at the Weizmann Institute of Science in Israel have identified an important molecular mechanism that may explain why some prostate cancers eventually become resistant to hormone therapy. The discovery could help researchers develop more personalized treatment strategies for patients with advanced prostate cancer. Weizmann Institute of Science
Prostate cancer growth is often driven by male sex hormones known as androgens. For this reason, androgen deprivation therapy and drugs that block androgen receptor signaling are widely used to treat advanced disease.
These treatments can be highly effective, but in many patients the cancer eventually adapts and begins progressing again. Understanding exactly how tumor cells bypass hormone blockade is therefore one of the major challenges in prostate cancer research.
An international research team led by Prof. Yosef Yarden of the Weizmann Institute investigated a genetic alteration involving the TMPRSS2 and ERG genes, which is found in approximately half of prostate cancers.
The researchers discovered that this gene fusion can allow cancer cells to switch from dependence on androgen signaling to another pathway involving cortisol and the glucocorticoid receptor. When standard treatment blocks androgen signaling, this alternative pathway may become activated and help tumor cells survive and continue growing. Weizmann Institute of Science
A Potential New Combination Treatment
The researchers tested their hypothesis in experimental models of human prostate cancer.
They found that simultaneously targeting androgen signaling and the glucocorticoid pathway was more effective at suppressing tumor growth than targeting either pathway alone. In mouse models, the combination also prolonged survival.
These findings suggest that the TMPRSS2-ERG gene fusion could potentially serve as a biomarker to identify patients who might benefit from a different therapeutic strategy.
The study also raises questions about the use of corticosteroids in certain patients with prostate cancer. Corticosteroids are used in several clinical situations, but according to the researchers, activation of the glucocorticoid pathway could potentially support tumor growth in cancers carrying this particular gene fusion. Weizmann Institute of Science
The findings were published in EMBO Molecular Medicine.
It is important to emphasize that this discovery does not immediately change the standard treatment of prostate cancer. Further clinical research will be necessary to determine whether blocking both pathways produces the same benefits in patients.
Nevertheless, the study provides another example of how molecular analysis of an individual tumor may help oncologists understand treatment resistance and potentially select more personalized therapies in the future.
If you have been diagnosed with prostate cancer, need a second medical opinion, or would like your case to be reviewed by Israeli specialists, contact Sapir Medical Clinic. We can help organize consultations with leading Israeli doctors, review and translate medical documents, arrange diagnostic examinations, and coordinate treatment in Israel.