RSPO2 (R-Spondin 2)

P2, N=8, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=60 --> 8

K-M plot analysis showed that patients with low RSPO2 expression have poor disease-free survival but could not be a risk factor. RSPO2 may be a potential biomarker for early-stage detection and provide valuable insight into the diagnosis of patients with CRC.

This ternary arrangement and forced dimerization of ZNRF3 likely underpin how LGR4 and RSPO2 potentiate Wnt/β-catenin signaling by sequestering ZNRF3 from Wnt receptors and facilitating its auto-inactivation. This study provides a structural basis for understanding the regulatory mechanism of Wnt/β-catenin signaling through the LGR4-RSPO2-ZNRF3 pathway and may offer opportunities for future drug development targeting this axis.

Peptibodies based on this RSPO2 furin mutant were conjugated with either pyrrolobenzodiazepine dimer or camptothecin derivative, and the resulting peptibodydrug conjugates (PDCs) showed potent and specific cytotoxic activity in neuroblastoma and colorectal cancer cell lines expressing any of LGR4/5/6 in vitro and robust anti-tumor activity in vivo. The results support the potential of RSPO2-based PDCs for the treatment of colorectal cancer, high-risk neuroblastoma, and other cancers that express LGR4/5/6.

Incorporation of PGAs from ctDNA into a CG model improved OS prediction by nearly 30% over a clinical model. This model can classify patients into risk groups and is useful for selecting patients in future mCRPC trials.

This study investigates the R-spondin family of genes (RSPO1/2/3/4), a group of secreted proteins that act as Wnt regulators, and their subsequent role in advanced prostate cancer (PC)...Conversely, this was not observed when CTNNB1 was overexpressed in the same models. These findings highlight that, in PC, RSPO2 functions as a unique member of the R-spondin family by promoting genes and signaling pathways associated with aggressive PC, and RSPO2 amplifications are associated with poor outcomes in PC patients.

Therefore, the article must be retracted. The authors were notified of this decision but did not respond.

The development of RSPO2-targeting nanobodies offers new prospects for treating RSPO2-related diseases. The nanobody serve as valuable tools for functional research and hold potential as diagnostic and therapeutic agents for RSPO2-driven conditions.

To investigate whether this interaction influences Wnt signaling in vitro, we conducted a Wnt signaling reporter assay (TOP Flash/FOP Flash) in neuroblastoma cells by introducing Rspo2, Wnt3a, and crizotinib, an ALK inhibitor. The results showed a decrease in the TOP/FOP ratio when ALK was inhibited. Collectively, our study reveals a novel role for ALK in enhancing Wnt signaling via R-spondins, providing new dimension into ALK-mediated oncogenesis.

Our findings highlight LMO1 and PRAME as potential biomarkers for identifying high-risk BC patients and informing targeted treatment strategies. This study provides valuable insights into the multi-omics landscape of BC and underscores the importance of personalized therapeutic approaches based on molecular profiles.

P=N/A, N=120, Recruiting, Shanghai East Hospital; Shanghai East Hospital

Analysis of transcriptome was performed for nine USP8-mutant and six USP8-WT adenomas and revealed the that the bidirectional dysregulation of Wnt signaling, including both the agonist RSPO2 and antagonist SFRP1, in the USP8-mutant corticotropinomas was downregulated. These alterations may indicate the existence of regulatory connections between USP8 enzyme activity, Wnt signaling, EGFR signaling and somatostatin receptors' trafficking, which can explain, at least in part, the clinical manifestations of CD in patients with corticotropinomas harboring USP8 variants.