Colorectal Cancer

In our cohort, the addition of MLPA provided an incremental yield of seven pathogenic CNVs, representing an 11.6% absolute increase in diagnostic sensitivity (from 16.7% to 28.3%) over the NGS-alone workflow, with CNVs accounting for 41% of all pathogenic findings. Our results show that MLPA is a very useful method in molecular diagnostics of LS and its implementation in routine genetic testing in combination with NGS using multigene panel testing would benefit both patients and health care providers.

Therapeutically, microbiota modulation via diet, metformin, and probiotics shows promise. Gut microbiota lies at the nexus of T2DM and CRC, functioning as a modifiable mediator rather than a passive bystander. Future research should prioritize longitudinal, multi-omic, and intervention-driven studies to enable personalized prevention and treatment strategies.

Human biomarker research is limited but indicates positive changes following interventions that increase UA. Future priorities include biomarker-driven, dose-finding trials stratified by metabotype, developing colon-targeted vs. systemic formulations, and testing combinations with chemotherapy and immunotherapy to determine safety and effectiveness.

Expression of these targets correlated with favorable clinical outcomes in CRC patients. This work provides the first comprehensive mechanistic insight into antisense oligonucleotide-mediated miRNA suppression in Caco-2 colorectal adenocarcinoma cells and expands the miRNA target landscape.

We have further demonstrated that these effects are partly mediated by the AhR, a mechanism that deserves further investigation. Future studies should build on these findings by (a) characterizing the specific mechanisms linking ROS production to apoptosis demonstrated in our model of exposure, (b) measuring the dynamics of the receptor following DEHP exposure and (c) examining these effects over a longer exposure period.

Notably, the model retained high accuracy in early-stage CRC (Stage I-II: AUC 0.929, 95% CI 0.868-0.989). Overall, this study provides a robust analytic framework for reproducible whole-blood RNA biomarker discovery and establishes a multi-gene signature with promising translational potential for minimally invasive and early CRC detection.

Among emerging therapies, the novel anti-angiogenic agent fruquintinib has recently demonstrated clinical efficacy in the treatment of mCRC. Based on the data discussed in the present narrative review, the therapeutic landscape of mCRC appears poised for significant evolution in the near future. While numerous challenges and unanswered questions remain, the emergence of innovative therapeutic combinations and agents provides a promising opportunity for improving patient outcomes in mCRC.

Correlation analysis demonstrated the best correlation with disease stage for CEA and weaker positive correlations for YKL-40, CA 19-9, and RLN2. These findings suggest that YKL-40 may serve as a useful adjunct serum biomarker for CRC diagnosis, especially when combined with conventional markers such as CEA.

We did not find any MP effects on the claudins, mucins, proapoptotic factor Bax, or on the proliferation marker Mki67 gene expression in the medial colon, nor on the serum level of TNFα, IL-1β, IL-6, and IL-10 cytokines. Thus, MPs promote the CAC development in mice by exacerbating intestinal local inflammation and damaging the epithelial barrier, and MPs may represent a potential environmental cofactor contributing to CAC risk.

In a triple-negative breast cancer model, we observed that 4-MU reduced spheroid volume and increased BRCA 1/2 levels, suggesting a potential mechanism of 4-MU for tumor shrinkage and BRCA restoration. These findings suggest that 4-MU, a compound already approved for oral use in hepatobiliary indications in Europe and Asia, is a mechanistically plausible HA-targeting candidate for therapeutic repurposing in BRCA-deficient tumors.

Furthermore, FBXW7 alterations contribute to chemoresistance and anti-EGFR therapy resistance but also reveal potential therapeutic vulnerabilities. These findings underscore FBXW7's promise as a prognostic biomarker and a potential target for precision oncology strategies in colorectal cancer.

P1, N=188, Recruiting, Alterome Therapeutics, Inc. | N=130 --> 188