Molecular Advances in Colorectal Cancer Care

Recent key publications

1. Endoscopist Adenoma Detection Rate Associated with Neoplasia Detection During Subsequent-Round Colonoscopy in Fecal Immunochemical Test-Based Colorectal Cancer Screening: Cross-Sectional Analysis of the SCREESCO Randomized Controlled Trial. Gastrointest Endosc. 2025 Feb 4:S0016-5107(25)00067-7. Sekiguchi M, Westerberg M, Lowbeer C, Forsberg A.

Link to full article:http://www.ncbi.nlm.nih.gov/pubmed/?term=39914632

The quality of initial colonoscopy in colorectal cancer screening programs using fecal immunochemical testing (FIT) may significantly impact outcomes in later screening rounds. Analyzing data from the large-scale SCREESCO randomized controlled trial reveals a strong correlation between endoscopists' adenoma detection rates (ADRs) and the identification of advanced neoplasia during second-round colonoscopies. These results emerge as global efforts intensify to optimize post-FIT surveillance protocols. These findings highlight the necessity of incorporating endoscopist performance metrics into follow-up strategies, especially as revised ADR benchmarks transform colorectal cancer screening standards worldwide.

2. Colonoscopy Findings After Increasing Two-Stool Faecal Immunochemical Test (FIT) Cut-Off: Cross-Sectional Analysis of the SCREESCO Randomized Trial. J Intern Med. 2024 Aug;296(2):187-199. Westerberg M, Eriksson J, Metcalfe C et al.

Link to full article:http://www.ncbi.nlm.nih.gov/pubmed/?term=38845164

As colorectal cancer (CRC) screening programs expand amid limited endoscopic resources, determining optimal fecal immunochemical test (FIT) cut-off thresholds becomes increasingly critical. This cross-sectional analysis from the SCREESCO randomized trial evaluates the clinical implications of raising the two-sample FIT cut-off threshold. Results show that higher thresholds substantially reduce colonoscopy demand while causing only modest decreases in advanced neoplasia and CRC detection rates. These findings provide valuable evidence for screening policy decisions, complementing international efforts to develop personalized screening approaches that effectively balance detection sensitivity against healthcare system capacity and resource limitations.

3. Circulating Tumor DNA as a Marker of Recurrence Risk in Stage III Colorectal Cancer: The α-CORRECT Study. J Surg Oncol. 2025 Jan 25. Diergaarde B, Young G, Hall DW et al.

Link to full article:http://www.ncbi.nlm.nih.gov/pubmed/?term=39865324

Circulating tumor DNA (ctDNA) shows promise as a biomarker for molecular residual disease (MRD) and recurrence risk in colorectal cancer, though prospective validation studies for stage III disease have been limited. This multicenter investigation applies a tumor-informed ctDNA assay to 124 patients, demonstrating significant prognostic value across post-surgical, post-treatment, and surveillance timepoints. The study reveals that ctDNA can predict cancer recurrence more than 10 months before radiologic detection and outperforms traditional carcinoembryonic antigen (CEA) monitoring. These findings emerge as global clinical trials including CIRCULATE-US and VEGA explore ctDNA-guided treatment approaches. The results provide valuable information for developing personalized surveillance protocols and optimizing adjuvant therapy decisions in colorectal cancer management.

4. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: 5-year outcomes of the randomized DYNAMIC trial. Nat Med. 2025 Mar 7. Tie J, Wang Y, Lo SN et al.

Link to full article:https://pubmed.ncbi.nlm.nih.gov/40055522/

Early data from the DYNAMIC study of circulating tumor DNA (ctDNA)-guided adjuvant chemotherapy (ACT) versus standard approach met its primary outcome demonstrating reduced ACT use without compromising 2-year recurrence-free survival (RFS) for stage II colon cancer. We report here other prespecified analyses of overall survival, ctDNA clearance and ctDNA level. At a median follow-up of 59.7 months, 5-year RFS was 88% and 87% with ctDNA-guided and standard management, respectively (difference 1.1%, 95% confidence interval -5.8% to 8.0%), and 5-year overall survival is similar (93.8% versus 93.3%, hazard ratio (HR) 1.05; P = 0.887). For treated ctDNA-positive patients, ctDNA clearance was observed at the end of ACT (EOT) in 35 out of 40 patients (87.5%). A higher than median postoperative tumor-derived mutant molecules per milliliter plasma was associated with worse 5-year RFS (HR 10.62; P = 0.005). For treated ctDNA-positive patients, post hoc analysis of ctDNA clearance at EOT assessed by a new assay that evaluated an average of 29 tumor-derived mutations per patient predicted for a favorable 5-year recurrence-free probability of 97% versus 0% for ctDNA persistence (P < 0.001). Mature DYNAMIC outcome data support a ctDNA-guided approach to ACT for stage II colon cancer, with potential to further risk stratify ctDNA-positive patients based on ctDNA burden and EOT results. Australian New Zealand Clinical Trials Registry Identifier: ACTRN12615000381583.

5. Feature Selection and Network-Driven Analyses to Unveil Common RNA Signatures in Colon and Pancreatic KRAS-Mutant Cancers. Cancer Med. 2025 Mar;14(5):e70468. Pane K, Zanfardino M, Grimaldi AM et al.

Link to full article:http://www.ncbi.nlm.nih.gov/pubmed/?term=40013338

KRAS mutations drive oncogenesis in both colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC), yet the molecular signatures shared between these cancers remain poorly understood. By integrating machine learning-based feature selection with network analysis, our study identified 70 common KRAS-associated gene signatures across CRC and PDAC using TCGA and CCLE datasets. Key molecular targets including MUC1, ITGA3, and PHLDA1 emerged as potential therapeutic candidates for precision oncology approaches. These findings illuminate convergent oncogenic mechanisms across different KRAS-driven cancers and provide a foundation for translational research targeting these shared pathways.

6. Progressive Plasticity During Colorectal Cancer Metastasis. Nature. 2025 Jan;637(8047):947-954. Moorman A, Benitez EK, Cambulli F et al.

Link to full article:http://www.ncbi.nlm.nih.gov/pubmed/?term=39478232

Understanding the dynamic phenotypic transitions underlying colorectal cancer (CRC) metastasis is crucial for developing improved therapeutic approaches. This Nature publication integrates matched trios of human samples—normal colon tissue, primary tumors, and metastases—with single-cell transcriptomics and organoid models to uncover a conserved trajectory of progressive cellular plasticity. The study identifies a critical fetal progenitor-like intermediate state that facilitates transition to non-canonical, therapy-resistant phenotypes, revealing an important but previously underexplored aspect of tumor evolution. As research increasingly focuses on targeting lineage plasticity to overcome treatment resistance, these findings offer timely and clinically relevant insights that could transform metastatic CRC management strategies.