CRC genetic mutational statuses as well as contributing environmental stress factors such as gut microbiota dysbiosis are prognostically crucial, associated with high risk potential of gene-environment interactions based on machine learning.

We implement an extended neoadjuvant regimen-typically a minimum of eight cycles of FOLFIRINOX-aiming for normalization of CA19-9 levels...IMV, inferior mesenteric vein; LGV, left gastric vein; SMA, superior mesenteric artery artery; SV, splenic vein; SMV, superior mesenteric vein; RHA, right hepatic artery Prioritizing tumor biology, meticulous preoperative planning, and attention to key vascular technical details to ensure radical resection represent our three core oncologic landmarks. Further international, multicenter studies are needed to validate and promote the standardization of surgery for BR-PC and LAPC.

Neoadjuvant chemotherapy prior to laparoscopic radical resection for rectal cancer was associated with improved anus preservation, enhanced postoperative recovery, and greater biochemical and functional benefits without increasing major complication rates, although it was linked to higher hematologic adverse events and postoperative declines in immune cell counts.

P3, N=129, Not yet recruiting, City of Hope Medical Center

FOLFOX (folinic acid, fluorouracil, and oxaliplatin) is a standard first-line therapy for microsatellite stable (MSS) CRC lacking actionable driver mutations; however, its efficacy and genomic impact in EOCRC, particularly in underrepresented groups, remain poorly understood. By integrating clinical, molecular, and treatment variables, the AI-HOPE and AI-HOPE-PI3K platforms enabled rapid, reproducible, and fine-grained analysis of complex datasets. These findings underscore the need for ancestry-informed molecular profiling to optimize therapeutic strategies and highlight AI-guided interrogation as a powerful tool for advancing precision oncology in underrepresented and disproportionately affected CRC populations.

P1, N=25, Completed, Massachusetts General Hospital | Active, not recruiting --> Completed

The addition of targeted therapy based on biomarker status (e.g., panitumumab in KRAS-wildtype tumors) demonstrated significant improvements in DFS and OS...Its efficacy is highly dependent on careful patient selection based on disease stage and molecular characteristics. Future research should focus on randomized trials in high-risk populations and the integration of personalized treatment approaches.

Simulations predict transitioning high-risk patients (CTC/tdEV score >1.75) to second-line FOLFIRI at week 4 or 10 improves median survival from 15.1 months (12.8-18.4 CI) to 22.7 months (17.1-35.8 CI), and from 13.3 months (10.5-21.7 CI) to 23.3 months (17.8-31.2 CI), respectively...These findings suggest that tdEVs, alone or in combination with CTCs, may help optimize treatment timing and outcomes in mCRC. The integration of CTCs and tdEVs into clinical practice could offer a personalized, cost-effective, and more sustainable alternative to routine imaging in managing advanced colorectal cancer.

P1, N=25, Recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Oct 2026 --> Oct 2027 | Trial primary completion date: Oct 2025 --> Oct 2026

HS was prognostic for RFS and OS in patients with resected stage III pMMR/MSS CC and associated with a trend toward improved RFS with the addition of cetuximab to adjuvant FOLFOX. Conversely, cetuximab seems detrimental in patients with GA tumors. These data may help to improve patient selection in future adjuvant clinical trials testing anti-EGFR therapies.

HPV-associated NECs may represent a distinct subset with better prognosis, but p16 is not a reliable surrogate marker. Routine subclassification into small vs. large cell types and comprehensive molecular profiling, including HPV testing, may aid clinical decision-making and prognostication.

JI-CJ002 augments the therapeutic effect of FOLFOX by suppressing DNA damage response and inducing aberrant cell cycle progression, thereby supporting its development as a chemo-sensitizing agent for colorectal cancer therapy.