Essential
- Researchers have noticed that the RSPO2 gene is linked to aggressive prostate cancer.
- In particular, it would promote the development of prostate tumors which do not depend on hormones for their growth.
- This discovery opens the way to a new therapeutic target.
Prostate cancer is known to be cancer progressing slowly with a “Good prognosis”. More than 9 out of 10 patients are alive 5 years after their diagnosis. But there are also aggressive and resistant forms of treatment, leaving patients little luck. It is on the understanding of these dangerous malignant tumors that researchers from the University of Minnesota-Twin Cities have just made a major step forward.
They identified a new gene linked to the disease. Their work was published in the journal Oncotarget July 25, 2025.
A gene promoting the spread of the tumor and resistance to treatments
Scientists focused on a group of genes coding R-Spondins proteins (RSPO1/2/3/4). The latter regulate, among other things, the WNT signaling pathway which is involved in the development of tumors.
By studying thousands of samples of prostate tumors, the team discovered that RSPO2 alterations were more frequent than those of other R-spondin genes or certain genes known to be involved in cancer (such as CTNNB1 and APC).
The analyzes have shown that they were present in more than 20 % of the metastatic prostate cancers. “Patients presenting these alterations had more aggressive signs of disease, including higher mutation rates and greater tumor complexity”specify the authors in their press release.
The work has also revealed that the expression of the RSPO2 gene increases the growth of cancer cells and triggers a biological process called the epithelio-mesenchymal transition (TEM). The latter is known to promote tumor spread and resistance to standard treatments. “Unlike other genes in the same way, RSPO2 also seemed to reduce the activity of androgens receptor genes, which suggests that it leads to a type of prostate cancer which does not depend on the hormones for growth.”
“These results emphasize that, in prostate cancer, RSPO2 works as a single member of the R-Spondin family by promoting the genes and signaling pathways associated with aggressive prostate cancer, and RSPO2 amplifications are associated with poor results in patients with prostate cancer”conclude the authors.
Prostate cancer: a discovery that brings a new therapeutic target
In addition, the researchers noticed that the RSPO2 protein had structural differences compared to other R-Spondins proteins. This could allow scientists to design drugs that specifically block their activity.
Thus, for the authors, the RSPO2 is “A promising therapeutic target, especially for patients who do not respond to existing hormonal treatments”. A track very little explored so far since there is no drug targeting RSPO2 still approved.
