From the Guidelines
Next-generation sequencing (NGS) is the preferred method for biomarker testing in metastatic colorectal cancer (mCRC), as it can detect rare and actionable genetic alterations, such as KRAS/NRAS and BRAF mutations, HER2 amplifications, and microsatellite instability (MSI)/mismatch repair (MMR) status, which guide treatment decisions. The role of NGS in colorectal cancer is multifaceted, including identifying genetic mutations that predict response to targeted therapies, such as EGFR inhibitors, and immunotherapies, like pembrolizumab or nivolumab 1. Some key points to consider when using NGS in colorectal cancer management include:
- NGS panels can be performed using either tissue or blood-based biopsies, allowing for flexibility in testing approaches 1
- Repeat molecular testing is not recommended after standard cytotoxic chemotherapy, unless there is a change in the molecular profile that may guide future targeted therapy decisions 1
- NGS can detect hereditary cancer syndromes, such as Lynch syndrome, through germline testing, enabling family screening and prevention strategies
- The technology also allows monitoring of circulating tumor DNA in blood samples to detect minimal residual disease and early recurrence NGS testing is typically performed on tumor tissue obtained during biopsy or surgical resection, with results available within 1-2 weeks, allowing oncologists to develop personalized treatment plans based on the specific molecular profile of each patient's cancer 1.
From the Research
Role of Next-Generation Sequencing in Colorectal Cancer
- Next-generation sequencing (NGS) is a comprehensive and efficient genomic profiling tool that guides personalized therapy for colorectal cancer 2.
- NGS has begun to supplant other technologies for genomic profiling, allowing for the detection of multiple genetic alterations with a minimum amount of DNA 3.
- The use of NGS in clinical practice has been shown to provide reliable and clinically relevant information for colorectal cancer patients, enabling personalized treatment decisions 4.
Detection of Genetic Mutations
- NGS can detect mutations in various genes, including KRAS, NRAS, BRAF, and PIK3CA, which are associated with resistance to certain therapies 2, 4, 5.
- The frequency of mutations can vary depending on the location of the tumor, with the right colon group showing a higher frequency of mutations 2.
- NGS can also detect concomitant mutations, such as PIK3CA mutations coexisting with KRAS, NRAS, or BRAF mutations 5.
Clinical Application of NGS
- NGS can aid in the prediction of responsiveness to therapeutic agents, such as cetuximab, and can identify patients who are more likely to benefit from targeted therapy 5.
- The use of NGS in clinical practice can improve targeted therapy prediction and enable more personalized treatment decisions 4, 5, 6.
- NGS has been compared to polymerase chain reaction (PCR) for detecting genetic mutations, showing high concordance between the two methods 6.