NCT07007689

A Multi-omics Study of BRAF V600E Mutant Colorectal Cancer

• Status: Not Yet Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 200 (estimated)
• Sponsor: Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This trial aims to elucidate the immune landscape and genetic basis of BRAF-mutant colorectal cancer (CRC) in Chinese patients by analyzing tumor tissue and peripheral blood. Single-cell RNA sequencing, T cell receptor (TCR) sequencing, proteomics and metabolomics, will be performed on tumor tissues, alongside TCR sequencing of peripheral blood, to establish a comprehensive immune and genetic profile of BRAF-mutant CRC. The study seeks to identify novel immune biomarkers, therapeutic targets, and signaling pathways, and to enable molecular subtyping for precision treatment and personalized management of BRAF-mutant CRC patients.

Detailed description

As an oncogenic gene, BRAF V600E subverts the need for continuous upstream activation and overcomes negative feedback signals that terminate pathway activation. In colorectal cancer, BRAF V600E mutations are associated with older age, right colon primary tumors and female gender, as well as reduced chemotherapy sensitivity and poor prognosis. In addition to a poor prognosis, BRAF V600E-mutant colorectal cancer is associated with a higher incidence of peritoneal metastasis, resulting in tumor-related symptoms such as pain, ascites, gastrointestinal and urinary obstruction, which severely compromise patients' quality of life. Although there is a trend that BRAF V600E mutant patients who receive high-intensity chemotherapy have longer progression-free survival (PFS), the prognosis of the BRAF V600E mutant population remains dismal and approximately 40% of patients do not respond to first-line high-intensity chemotherapy. In addition, the response rate of combined targeted therapy is limited to around 25% and the duration of anti-epidermal growth factor receptor (EGFR) and anti-BRAF is around 4 months due to the presence of bypass activation. What's more, patients with BRAF V600E mutation and mismatch repair-proficient (pMMR) also had a poor response to anti-programmed death-1 (PD-1) therapy. The tumor heterogeneity and tumour immune microenvironment of BRAF V600E mutant colorectal cancer need to be investigated. The study seeks to identify novel immune biomarkers, therapeutic targets, and signaling pathways, and to enable molecular subtyping for precision treatment and personalized management of BRAF-mutant CRC patients.

Conditions

• BRAF V600E-mutant Metastatic Colorectal Cancer

Timeline

• Start date: 2025-07-01
• Primary completion: 2027-12-31
• Completion: 2027-12-31
• First posted: 2025-06-06
• Last updated: 2025-06-06