September: 53 year-old man with Metastatic Colorectal Cancer

Case description:

A 53 year-old man was diagnosed with metastatic colorectal cancer.

In 2023, the primary sample was tested using our OncoDEEP® Kit. The analysis revealed a FMN1-NTRK3 gene fusion for this patient and a positive HRD score for this patient.

Clinical interpretation:

Multiple studies have shown that patients with tumors harboring mutations in KRAS or NRAS exons 2, 3, or 4 predict lack of response to anti-EGFR antibody therapy given in combination with chemotherapy (PMID: 24942275). In the present case, we showed that the patient is wild type for KRAS and NRAS meaning that he should be sensitive to anti-EGFR therapy (e.g. FDA approved EGFR therapy in colorectal cancer : cetuximab and panitumumab).

Moreover, we highlighted the presence of a FMN1-NTRK3 gene fusion. NTRK rearrangements represent the molecular driver of a subset of solid tumors, (PMID: 28444624) which is found at low frequencies (commonly <1%) (PMID: 31803506) and who lead to transcription of chimeric TRK proteins with constitutively activated or overexpressed kinase function that confers oncogenic potential (PMID: 27843590). Entrectinib and larotrectinib, are two receptor tyrosine kinase inhibitors FDA approved in solid tumors that have a NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy. These drugs are thus an additional therapeutical option for this patient.

Finally, we observed a positive HRD scoring for this patient. Deficiency in HRR (HRD) is a target for PARP inhibitors. Even if we cannot make any conclusion about the benefit of PARP inhibitor in colorectal cancer, some clinical trials are recruiting. (Read also Homologous Recombination Deficiency assessment for clinical management using the OncoDEEP® Kit).

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