New Target Identified in aggressive prostate Cancer: RSPO2 Gene Shows Promise for Future Therapies
MINNEAPOLIS, MN – July 26, 2025 – Researchers at the university of Minnesota-Twin Cities have pinpointed a gene, RSPO2, as a key driver of aggressive, hormone-resistant prostate cancer, offering a potential new avenue for treatment progress.The findings, published today in Oncotarget, reveal that alterations in RSPO2 are surprisingly common in advanced prostate cancer and correlate wiht more aggressive disease characteristics.
Prostate cancer remains the most frequently diagnosed cancer in American men. While initial treatment frequently enough involves hormone therapy targeting the androgen receptor, many patients ultimately develop resistance, leading to disease progression and poorer outcomes. This new research focuses on understanding the mechanisms behind this resistance and identifying novel therapeutic targets.
The study, led by Aiden Deacon and Justin Hwang, investigated the role of the R-spondin family of genes (RSPO1/2/3/4) – known regulators of the Wnt signaling pathway – in metastatic prostate cancer. Analyzing thousands of tumor samples, the team discovered that alterations in RSPO2 were more prevalent than changes in other R-spondin genes, and even surpassed the frequency of alterations in well-established cancer genes like CTNNB1 and APC. Specifically, RSPO2 amplification was observed in over 20% of metastatic prostate cancer cases.
Patients exhibiting thes RSPO2 alterations demonstrated more aggressive disease features, including higher mutation rates and increased tumor complexity. Laboratory experiments further revealed that RSPO2 boosts cancer cell growth and initiates epithelial-mesenchymal transition (EMT), a process that facilitates tumor spread and resistance to conventional treatments.
Notably, RSPO2 appears to operate independently of the androgen receptor, actively reducing the activity of androgen receptor genes. This suggests that RSPO2 drives a subtype of prostate cancer that has become less reliant on hormones for growth, explaining resistance to standard hormone therapies. Researchers observed that RSPO2 overexpression in cell lines led to increased expression of EMT-related transcription factors, including ZEB1, ZEB2, and TWIST1.
“Current therapies targeting the Wnt pathway are limited, and there are no approved drugs that specifically inhibit RSPO2,” explains the research. However,the study highlights the unique structural characteristics of RSPO2,suggesting the possibility of developing targeted drugs to block its activity.
this research provides crucial insight into the development and persistence of aggressive prostate cancer and identifies RSPO2 as a promising therapeutic target, particularly for patients who have stopped responding to hormone-based treatments. The findings open the door to future research focused on developing therapies specifically designed to combat RSPO2-driven prostate cancer, potentially improving outcomes for those with advanced disease.
Source: Deacon, A., et al. (2025). Dissecting the functional differences and clinical features of R-spondin family members in metastatic prostate cancer. Oncotarget. doi.org/10.18632/oncotarget.28758.
