Colorectal Cancer

P=N/A, N=90, Recruiting, Vejle Hospital | Not yet recruiting --> Recruiting

P=N/A, N=60, Recruiting, West China Hospital

P=N/A, N=55, Active, not recruiting, University of Chicago | Trial completion date: Oct 2025 --> Oct 2027 | Trial primary completion date: Oct 2025 --> Oct 2027

P=N/A, N=388, Recruiting, University Health Network, Toronto | Trial completion date: Aug 2025 --> Nov 2026 | Trial primary completion date: May 2025 --> Jun 2026

P=N/A, N=400, Not yet recruiting, Fudan University

P=N/A, N=600, Completed, Wake Forest University Health Sciences | Active, not recruiting --> Completed

P1, N=27, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Aug 2025 --> Jun 2027 | Trial primary completion date: Aug 2025 --> Jun 2027

P=N/A, N=100, Not yet recruiting, Fred Hutchinson Cancer Center | Initiation date: Aug 2025 --> Dec 2025

P1, N=31, Terminated, Shanghai Junshi Bioscience Co., Ltd. | N=198 --> 31 | Recruiting --> Terminated; The trial was stopped early on the initiative of the sponsor on the basis of a change in the research and development strategy without safety concerns

We show that GDF15 secretion upregulates the glycolytic enzyme ENO1 in cancer cells, which triggers extracellular lactate release and subsequent lactylation of H4K8 in CECs, augmenting GDF15 transcription. Our findings establish a mode of intercellular crosstalk mediating collaboration between colorectal cancer cells and peritumoral CECs, providing a potential avenue for targeted intervention in colorectal cancer.

Here, by mediating transformation on different mouse backgrounds containing mutations in Kras or other common CRC driver genes, we establish that the presence of diverse priming events in the normal mouse intestinal epithelium can change the transformation and clonal-selection landscape, permitting the fixation of strong driver mutations in Apc and Ctnnb1 that are otherwise lost due to negative selection. These findings, combined with our demonstration of mutational patterns consistent with similar priming events in human CRC, suggest that the order in which driver mutations occur in intestinal epithelium can determine whether clones are positively or negatively selected and can shape subsequent tumour development.

Individual patient data (IPD) from the KEYNOTE-177 and CheckMate-8HW trials were collected with IPDfromKM and used to develop a Markov model with a 30-year duration and three mutually exclusive health states, providing a framework for the evaluation of the cost-effectiveness of first-line nivolumab together with ipilimumab, pembrolizumab, and chemotherapy for treating MSI-H/dMMR advanced CRC. In addition, the established model is stable. First-line immunotherapeutic treatments for MSI-H/dMMR advanced CRC cases in the USA appears to be cost-effective, with a dual-immunotherapeutic regimen consisting of nivolumab plus ipilimumab being preferable.