Prof Hans Prenen, medical oncologist at UZA in Antwerp, delivered a lecture elucidating the pertinent biomarkers in metastatic colon cancer (mCRC). Unlike well-established subtypes in breast and lung cancers, classifying mCRC would be advantageous. Various classification methods exist; however, focusing on genomic rather than methylation-level analysis is imperative for clinical relevance.
Certain tumours exhibit elevated mutation rates, particularly in MSI-High cancers, indicating potential responsiveness to immunotherapy. Additionally, patients with early-stage POLE mutations demonstrate exceptionally favourable prognoses. Gene expression levels provide insights into tumour biology and prognosis, though they do not presently guide therapy selection.
In current clinical practice, essential biomarkers for mCRC include broad next-generation sequencing (NGS) covering classical parameters like RAS and BRAF mutations. Further exploration of markers within the AKT pathway may be relevant. Hyperselecting patients with wild-type RAS enhances anti-EGFR response. If no oncogenic driver is identified, fusion panels are recommended.
MSI testing is crucial, with standard PCR and immunohistochemistry being preferred methods due to validation concerns in NGS. MSI-high patients should be screened for fusions, albeit they are rare in this subset.
HER2 amplifications, an emerging marker, should be tested early in metastatic cases, offering insights into resistance to anti-EGFR therapy. Validation of HER2 amplification methods and cut-offs is essential. Higher copy numbers correlate with superior responses to anti-HER2-targeted agents. Coexistence with RAS mutations’ significance requires further elucidation in this context.
In summary, mCRC patients should undergo testing for RAS, BRAF, MSI, HER2, and fusions. Sequential testing is practical; once a RAS mutation is identified, further fusion analysis may not be necessary. Precision in specifying RAS mutations, such as G12C and G12D types, will become increasingly vital with the emergence of specific RAS-targeted therapies.
With the educational support of:
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