Colorectal Cancer

P2, N=50, Recruiting, Zhejiang University | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

P2, N=21, Completed, First Affiliated Hospital, Sun Yat-Sen University | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P=N/A, N=15, Not yet recruiting, Fundacion Arturo Lopez Perez

P=N/A, N=8000, Recruiting, UMC Utrecht | Trial completion date: May 2025 --> Aug 2030 | Trial primary completion date: Feb 2024 --> Feb 2030

COL8A1⁺Fibs orchestrate 5-FU resistance in CRC via a COL8A1/ITGB1-mediated EMT axis. Disrupting this stromal-tumor crosstalk represents a promising therapeutic strategy to overcome chemoresistance.

Fluorouracil induced an E2F4/SETD1A/METTL3 regulatory axis, wherein E2F4 self-regulation activated SETD1A to drive METTL3 methylation. Targeting this axis through pharmacological inhibition of E2F4 or genetic disruption of METTL3 methylation cooperated with immune checkpoint blockade (ICB) to significantly suppress tumor growth. These findings unveil a methylation-dependent regulatory mechanism that reshapes the tumor immune microenvironment, offering a therapeutic strategy for CRC.

Genetic or pharmacological inhibition of PKM2 lactylation disrupted VM and synergized with bevacizumab in patient-derived pre-clinical models, significantly improving therapeutic efficacy. Together, this study reveals lactylation as a metabolic switch linking cancer glycolytic reprogramming to transcriptional rewiring and proposes targeting PKM2 lactylation to enhance the anti-tumor activity of bevacizumab in CRC.

Adagrasib monotherapy yielded a median PFS of 4.4-5.6 months, an OS of 10-19.8 months, and an ORR of 19-23%, while its combination with cetuximab reported a PFS of 6.9 months, an OS of 13.4-15.9 months and an ORR of 34-46%...When combined with panitumumab, 960 mg sotorasib demonstrated better results with a PFS of 5.6-5.7 months, OS of 15.2 months and an ORR of 12.5-30%. Similarly, divarasib monotherapy led to a PFS of 5.6-6.9 months and an ORR of 20%, while its combination with cetuximab resulted in a PFS of 8.1 months and an ORR of 62.5%. Combination therapy of olomorasib and MK-1084, which are new-generation KRAS p.G12C (c.34G > T) inhibitors, with cetuximab also demonstrated highly promising efficacy with ORR of 38-44% and 50%, respectively...Initial results of KRAS-G12C inhibitors appear highly promising when they are combined with anti-EGFR therapy compared to historical therapeutic agents indicated for patients with chemotherapy-refractory CRC. Encouraging benefits warrant frontline trials with these novel therapeutics.

Furthermore, the platform was extended to achieve site-specific m6A quantification, revealing upregulated methylation at specific sites of CDCP1 mRNA in bladder cancer cells and let-7a-5p miRNA in colorectal cancer cells compared with normal epithelial cells. Overall, this IDNP-mediated nFCM assay platform provides a powerful and versatile approach for rapid, simple, and multiplexed biochemical analysis, showing broad potential in biomedical and clinical applications.

P=N/A, N=700, Active, not recruiting, Blokhin's Russian Cancer Research Center

Additionally, it exhibits excellent biocompatibility in vitro and in vivo. Overall, this work presents a novel nanomedicine, siAURKB-loaded MSN, highlighting its surface modification with ionizable amino groups, which offers a promising therapeutic paradigm for CRC.