CCND1 (Cyclin D1)

P1/2, N=27, Recruiting, OHSU Knight Cancer Institute | Not yet recruiting --> Recruiting

In CRC, however, SLC46A1 downregulation induces intracellular folate deficiency, triggering locus-specific DNA hypomethylation at the FOS promoter, which activates oncogenic transcription of key downstream effectors (CCND1, BCL2, PLAU), driving tumor progression. The graphical abstract illustrates the differential impact of SLC46A1 on folate metabolism and gene expression in normal versus tumor cells, highlighting its potential as a therapeutic target in CRC.

8d also induced cell apoptosis through the mitochondrial pathways, as evidenced by alterations in the expressions of pertinent proteins, including Bcl-2 and Bax. These results indicated that the novel spirotetramine derivative 8d is a potential anti-cancer candidate drug and provides a new structural basis for the development of anti-cancer drugs.

This led to the downregulation of key oncogenic effectors including Slug, FN1, CDH2, F2RL1, CDK6, CCND1, MMP9, CDKN2A, and SQSTM1, while upregulating tumor suppressors CDKN1B, CDKN1A, and DDIT3. In conclusion, COPB2 acts as an oncogene in GC, driving tumor progression through modulation of the cell cycle and key signaling pathways, highlighting its potential as a therapeutic target.

Our findings suggest that Res may regulate BCa cell expression through the AURKA/STAT3 axis, providing a theoretical foundation for the structural optimization of Res and the development of multi-target drugs for clinical application.

However, adjuvant chemotherapy significantly led to better overall survival. The Hippo pathway is frequently deregulated (nuclear YAP/TAZ in 61.4% of patients), suggesting it is a compelling novel therapeutic target for this aggressive disease.

This study provides the first evidence of molecular changes in peritumour tissue to demonstrate field effect in PeSCC, characterised by downregulation of Wnt4, upregulation of c-MYC, and altered spatial colocalisation of Wnt-related proteins in cancer-adjacent skin. These findings suggest that peritumoral tissues exhibit early molecular alterations that extend beyond the morphologically defined tumour margin. Recognising these changes may have implications for understanding tumour microenvironment conditioning and for the future development of biomarkers relevant to margin assessment in penile carcinogenesis.

P1/2, N=54, Terminated, Incyte Corporation | Completed --> Terminated; A business decision was made to discontinue further enrollment. There were no safety concerns that contributed to this decision.

After a delay, contact inhibition suppresses YAP activity, which gradually downregulates mitogen signaling and the cyclin D1/p27 ratio. Thus, critical for regeneration without cancer initiation, robust proliferation responses result from a YAP-induced and receptor-mediated prolonged increase in the cyclin D1/p27 ratio, which is reversed by delayed suppression of receptor signaling after contact inhibition of YAP.

This study clarified ECSIT's dual role in stabilizing β-catenin and sustaining Wnt signaling-regulating Lgr5 intestinal stem cell proliferation and differentiation, epithelial renewal, and immune balance. These findings offer insights into CIM pathogenesis and establish the basis for developing targeted therapy through ECSIT-Wnt axis regulation.

Our study identified PLK1 as a key regulator of β-catenin signaling flexibility in CRC, coordinating kinase-dependent and transcriptional mechanisms to sustain pathway activation. The discovery of the PLK1-NFKB2-USP2a-β-catenin axis provides a novel therapeutic rationale for targeting PLK1 to selectively disrupt Wnt-driven tumorigenesis, potentially overcoming the toxicity limitations of conventional Wnt inhibitors.

This study demonstrates the therapeutic efficacy of restoring the imbalanced expression of miRNA in the liver. Therefore, the clinical translation of this miRNA-based strategy warrants further investigation.