Related Experiment Video
Updated: Jul 5, 2025
Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
A Phase II Exploratory Study to Identify Biomarkers Predictive of Clinical Response to Regorafenib in Patients with
Karen Gambaro1,2,3, Maud Marques1,3, Suzan McNamara1,2
1Canadian National Centres of Excellence-Exactis Innovations, Montreal, QC H3T 1Y6, Canada.
Abstract:
Single-agent regorafenib is approved in Canada for metastatic colorectal cancer (mCRC) patients who have failed previous lines of therapy. Identifying prognostic biomarkers is key to optimizing therapeutic strategies for these patients. In this clinical study (NCT01949194), we evaluated the safety and efficacy of single-agent regorafenib as a second-line therapy for mCRC patients who received it after failing first-line therapy with an oxaliplatin or irinotecan regimen with or without bevacizumab. Using various omics approaches, we also investigated putative biomarkers of response and resistance to regorafenib in metastatic lesions and blood samples in the same cohort. Overall, the safety profile of regorafenib seemed similar to the CORRECT trial, where regorafenib was administered as ≥ 2 lines of therapy. While the mutational landscape showed typical mutation rates for the top five driver genes (APC, KRAS, BRAF, PIK3CA, and TP53), KRAS mutations were enriched in intrinsically resistant lesions. Additional exploration of genomic-phenotype associations revealed several biomarker candidates linked to unfavorable prognoses in patients with mCRC using various approaches, including pathway analysis, cfDNA profiling, and copy number analysis. However, further research endeavors are necessary to validate the potential utility of these promising genes in understanding patients' responses to regorafenib treatment.
Insights
Regorafenib is effective for metastatic colorectal cancer (mCRC) after initial therapy. Biomarker research identified KRAS mutations linked to resistance, suggesting potential for personalized treatment strategies in mCRC patients.
Area of Science:
- Oncology
- Genomics
- Pharmacology
Background:
- Metastatic colorectal cancer (mCRC) treatment requires effective therapies after initial treatment failure.
- Identifying prognostic biomarkers is crucial for optimizing therapeutic strategies in mCRC.
- Regorafenib is approved in Canada as a single agent for pre-treated mCRC patients.
Purpose of the Study:
- To evaluate the safety and efficacy of regorafenib as a second-line therapy for mCRC.
- To investigate biomarkers of response and resistance to regorafenib using omics approaches.
- To explore genomic-phenotype associations for predicting patient outcomes.
Main Methods:
- Clinical study (NCT01949194) evaluating regorafenib in mCRC patients post-first-line therapy.
- Multi-omics approaches including cfDNA profiling and copy number analysis.
- Analysis of metastatic lesions and blood samples for biomarker identification.
Main Results:
- Regorafenib demonstrated a safety profile consistent with previous trials.
- KRAS mutations were found to be enriched in intrinsically resistant lesions.
- Several potential biomarker candidates linked to unfavorable prognoses were identified.
Conclusions:
- Regorafenib shows promise as a second-line treatment for mCRC.
- KRAS mutations may indicate intrinsic resistance to regorafenib.
- Further research is needed to validate identified biomarkers for clinical utility in mCRC.
More Related Videos
09:29Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
07:59Portal Vein Injection of Colorectal Cancer Organoids to Study the Liver Metastasis Stroma
Published on: September 3, 2021