ZNRF3 (Zinc And Ring Finger 3)

Despite multiple adverse prognostic indicators, the patient has remained disease-free for over 5 years following adrenalectomy and adjuvant low-dose mitotane therapy. These findings suggest that GNAS activation may drive steroidogenesis while attenuating malignant progression, as demonstrated by integrated morphologic and genomic assessment in this case.

P1, N=70, Active, not recruiting, Eisai Co., Ltd. | Trial completion date: Jan 2026 --> Mar 2027 | Trial primary completion date: Jan 2026 --> Mar 2027

Integration of Wnt-centric gene signatures and machine-learning risk models now enables patient stratification and outcome prediction. Targeting context-dependent Wnt signaling, combined with rational combinatorial immunotherapy and TME reprogramming, offers a promising precisiononcology strategy to overcome therapeutic barriers in Wnt-driven malignancies.

AR alterations in ctDNA accumulate at progression in mCRPC patients treated with ARPIs, especially in those with initially durable responses. These findings support the use of liquid biopsy to serially track resistance mechanisms and inform precision therapy in advanced prostate cancer.

Mechanistically, RSPO4 exerted suppressive effects on Wnt signaling in an LGR4/5- and ZNRF3- dependent manner, through promoting LRP6 degradation and ZNRF3 stabilization. Our study revealed a novel role of RSPO4 as a tumor suppressor through antagonizing Wnt signaling, which provides important implications for development of diagnostic biomarkers and targeted therapy.

Moreover, overexpression of both RNF43 and HUNK was associated with prolonged OS compared to the overexpression or unaltered expression of HUNK alone. Conclusion Collectively, these results suggest RNF43 and AXIN2 as favorable prognostic factors and HUNK as a poor prognostic factor and therapeutic target for patients with GC.

RNF43 is a CRC predisposition gene, but risks are moderate, the reported polyposis phenotype is often absent and molecular phenocopies can occur. N-terminal germline RNF43 variants confer higher risk, although weak effects of C-terminal variants cannot be excluded. Genetic testing and patient management should incorporate these factors.

Gastric tumors can bypass niche dependence by acquiring KRAS-MAPK-SMAD2/3-driven epithelial WNT secretion. Targeting this axis-through MAPK inhibition, SMAD2/3 blockade, or suppression of WNT secretion-may represent a therapeutic vulnerability in gastric cancer and other KRAS-high malignancies.

These findings define a new regulatory axis linking the pro-WNT activity of WNKs to RNF43/ZNRF3-mediated feedback inhibition. Targeting WNK now offers a novel therapeutic strategy to restore WNT pathway control in cancers with RSPO fusions or RNF43 mutations.

The obtained results indicate that the lack of MCPIP1 RNase activity activates genes and processes associated with the migratory activity of cancer cells. In summary, the results obtained in this doctoral thesis indicated that MCPIP1 may regulate the progression of clear cell renal cancer at various levels of proangiogenic and prometastatic factors, as well as by influencing the EMT process.

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

The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 43: 1817‑1829, 2019; DOI: 10.3892/ijmm.2019.4107].