Primary and Acquired Resistance to Targeted Treatment in BRAF V600E-mutated Metastatic Colorectal Cancer (PARTACER-Suisse)
This study prospectively investigates the molecular mechanisms of primary and acquired resistance to standard-of-care BRAF V600E-directed therapy in patients with metastatic colorectal cancer and aims to pre-clinically develop novel strategies to reverse therapy resistance. Clinically approved combination treatment with cetuximab, encorafenib and chemotherapy improves patient outcomes, yet patients eventually experience disease progression. In this prospective multicenter study, tumor tissue, blood, and stool samples will be collected before treatment and at progression, to identify genetic and non-genetic mechanisms of resistance. Additionally, tumor tissue-based in vitro models (patient-derived organoids, PDOs) will be generated and exploited for functional in vitro testing, including genomic and pharmacologic perturbation studies. The overarching goal is to generate knowledge that can help develop new and more effective treatment strategies for future patients.
• Diagnosis of unresectable or metastatic BRAF V600E-mutated colorectal cancer
• Planned initiation of treatment with combined anti-EGFR antibody and BRAF inhibitor
• Patients receiving treatment in any line, with or without chemotherapy
• At least one tumor lesion accessible for biopsy
• ECOG performance status 0-2
• Life expectancy of at least 3 months
• Age ≥18 years
• Ability to provide written informed consent