◆ TRIAL DATA

Adding celecoxib to immunotherapy increases complete response in MSI-H colorectal cancer — Lancet Oncology

A phase 2 trial tested whether adding celecoxib (a COX-2 inhibitor) to the immunotherapy drug toripalimab would improve outcomes in patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) locally advanced colorectal cancer before surgery. The PICC-2 trial enrolled patients aged 18-75 years with clinical stage T3-T4 or any clinical T stage with lymph node involvement at three academic hospitals in China. Preclinical studies suggested that COX-2 inhibition might modulate the inflammatory tumor microenvironment and enhance the effect of PD-1 blockade.

▪ SCREENING

Blood test detects colorectal cancer recurrence earlier than imaging in stage III patients — Cancer Diagnosis & Prognosis

A retrospective case series of four patients with stage III colorectal cancer demonstrated the clinical utility of the Signatera assay, a personalized circulating tumor DNA (ctDNA) test. The assay detected minimal residual disease (MRD) and predicted recurrence earlier than traditional imaging scans. Signatera is a tumor-informed ctDNA test that reports results in mean tumor molecules per milliliter (MTM/ml), offering dynamic monitoring beyond traditional mutant allele frequency methods.

▸ TREATMENT

Re-challenging BRAF V600E tumors with encorafenib, cetuximab, and nivolumab shows success — Clinical Colorectal Cancer

A case report from the AGMT mCRC Registry documented successful re-challenge with encorafenib and cetuximab combined with nivolumab in a patient with BRAF V600E mutated, mismatch-repair-proficient (pMMR) metastatic colorectal cancer. This case suggests that adding immunotherapy to targeted therapy may restore sensitivity even after prior progression.

◆ TRIAL DATA

Alpelisib plus capecitabine shows modest activity in PIK3CA-mutant metastatic colorectal cancer — Scientific Reports

A phase 2 study tested alpelisib (a PI3K inhibitor) combined with capecitabine in 26 patients with PIK3CA-mutant metastatic colorectal cancer who had progressed after standard chemotherapy. The trial was conducted across nine institutions. Median progression-free survival was 3.5 months and overall survival was 8.8 months, with partial responses observed in two patients and disease control achieved in more than half of the cohort. Clinical benefit was more frequently observed in patients without KRAS mutations or liver metastases. Hyperglycemia was the most common adverse event.

◇ RESEARCH

Scientists identify metabolic pathway driving cetuximab resistance — Cell Death & Disease

Researchers discovered that glutamate dehydrogenase 1 (GDH1) accumulation drives cetuximab resistance in metastatic colorectal cancer. When cetuximab blocks EGFR, it prevents phosphorylation of GDH1, leading to its accumulation and increased production of α-ketoglutarate (αKG). This metabolic change remodels the tumor immune microenvironment to suppress immune responses. GDH1 depletion sensitized CRC cells to cetuximab and suppressed remodeling of the tumor immune microenvironment, as revealed by single-cell RNA sequencing.

◇ RESEARCH

Irisin enhances 5-fluorouracil effectiveness in colon cancer cells — International Journal of Applied and Basic Medical Research

Human HT-29 CRC cells were treated for 12 hours with irisin (2, 20, and 200 ng/mL) alone or combined with 5-FU (50 μM). Cell cycle progression and apoptosis were assessed by flow cytometry. Expression of cell cycle regulators (CCND1, CCND3, p21, and p27), apoptotic markers (BCL2, Bcl-2-associated X protein, cytochrome c, caspase-8, caspase-9, and caspase-3), and metabolic mediators (protein kinase B [Akt], mammalian target of rapamycin [mTOR], adenosine monophosphate-activated protein kinase) were assessed.

◇ RESEARCH

CT radiomics identifies imaging biomarkers in RAS-mutant metastatic colorectal cancer — European Journal of Radiology

Researchers established a co-clinical computed tomography (CT) radiomics pipeline for identifying candidate imaging biomarkers in RAS-mutant metastatic colorectal cancer. Orthotopic KRAS-mutant xenograft models (LOVO-Luc2 and SW480-Luc2, N=52 each) were treated with standard-of-care regimens (FOLFOX, bevacizumab, or combination) and longitudinally imaged by CT (N=104 tumour scans, N=156 liver scans over 4 timepoints). Radiomic features derived from primary tumour and liver parenchyma were assessed as biomarkers of treatment sensitivity and early metastatic disease. Pre-treatment CT-radiomics identified baseline radiomic correlates of treatment sensitivity in the LOVO-Luc2 model (0.716), with first-order statistical features (Median, 10percentile) significantly associated with response.

◇ RESEARCH

Researchers question whether lymph node removal may impair immunotherapy response — Colorectal Disease

A hypothesis-generating review examines whether routine lymphadenectomy (removal of ≥12 lymph nodes, a well-recognized quality indicator in colorectal cancer surgery) may theoretically impair systemic immune surveillance and immune checkpoint inhibitor (ICI) response. The authors reviewed surgical, oncological and immunological literature, including comparisons to breast cancer and melanoma where sentinel lymph node biopsy (SLNB) is used. The concern is most applicable to mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) disease. Contemporary immunology reframes tumor-draining lymph nodes (TDLNs) as active coordinators of anti-tumor immunity.