Association Between Intratumoral Fusobacterium Nucleatum Burden and Therapeutic Resistance to Anti-EGFR Monoclonal Antibodies in Metastatic Colorectal Cancer: An Integrated Analysis of Clinical and Molecular Data
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 500
- Locations
- 1
Study Overview
Brief Summary
This retrospective observational cohort study investigates the association between the intratumoral burden of the bacterium Fusobacterium nucleatum (Fn) and the efficacy of anti-EGFR targeted therapies (cetuximab or panitumumab) in patients with RAS wild-type metastatic colorectal cancer (mCRC). Bacterial quantification will be performed using droplet digital polymerase chain reaction (ddPCR) on formalin-fixed, paraffin-embedded (FFPE) tissue samples, comprising an estimated cohort of 500 patients.
Detailed Description
RAS wild-type colorectal cancer is frequently treated with anti-EGFR monoclonal antibodies; however, primary and acquired resistance rates remain a major limitation to clinical outcomes. Recent evidence suggests that Fusobacterium nucleatum colonization acts as a resistance factor to conventional chemotherapy through the induction of autophagy. This project aims to address the current scientific gap regarding the impact of this bacterium on the response to EGFR inhibitors. The study includes absolute quantification of bacterial 16S ribosomal RNA by droplet digital polymerase chain reaction (ddPCR) and its association with clinicopathological variables, overall survival, progression-free survival, and molecular profile (BRAF, TP53, PIK3CA, and MSI). Additionally, in an exploratory approach, the study will perform a comparative investigation of microbial colonization dynamics between primary tumor sites and their corresponding metastatic lesions using paired tissue samples.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Retrospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically confirmed diagnosis of metastatic (Stage IV) adenocarcinoma of the colon or rectum.
- •Received at least one cycle of anti-EGFR therapy (cetuximab or panitumumab), either as monotherapy or in combination regimens, regardless of the line of therapy.
- •Anti-EGFR therapy administered between January 2016 and December
- •Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks (from primary tumor or metastatic site) stored in the institutional biobank, with adequate quality for molecular analysis
Exclusion Criteria
- •Primary tumor originating in sites other than the colon or rectum.
- •Presence of activating mutations in KRAS or NRAS genes.
- •Presence of BRAF gene mutation (except for patients who received anti-EGFR therapy combined with BRAF inhibitors, according to standard clinical practice for this subgroup).
- •Tumor histology other than adenocarcinoma.
- •Insufficient clinical or follow-up data in medical records for the evaluation of the study's primary endpoints
Investigators
Leticia Dias Costa
Principal Investigator
Barretos Cancer Hospital