NTRK fusion

These findings highlight the value of RNA-based NGS, particularly when used alongside DNA NGS, to provide a comprehensive assessment of NTRK fusions and co-occurring gene alterations. Implementation of combined DNA and RNA CGP in a community health system setting enables detection of both known and novel NTRK fusions and can inform clinical care of cancer patients.

NTRK gene fusions are a critical marker for pediatric soft tissue tumors and are used for precision medicine in these tumors. NTRK gene fusions are used as diagnostic markers for infantile fibrosarcoma, congenital mesoblastic nephroma, and secretory carcinomas, and they play a critical role in the management of these tumors.

Many repotrectinib AEs, including neurological AEs secondary to TRK inhibition, were mitigated with appropriate management, including dose modification and/or pharmacologic intervention.

P1/2, N=174, Recruiting, Tubulis GmbH | N=120 --> 174

Functional NTRK fusion-positive tumors comprise biologically and clinically distinct subsets defined by tumor type and MSI/TMB context. Concurrent reporting of MSI/TMB (and HRD/EBV when available) together with NTRK fusion status may facilitate integrated clinical interpretation, support precision treatment selection, and refine trial stratification in clinical practice.

Comprehensive molecular analysis and MTB discussion revealed several potential treatment targets, leading to subsequent treatment including dinutuximab beta, nivolumab, cabozantinib, I-131-mIBG radionuclide therapy and alpelisib, unfortunately, all followed by disease progression. This case demonstrates the potential of comprehensive molecular analysis including methylation profiling for diagnosis and treatment guidance in rare tumors. Additional research is urgently required to improve outcomes in elderly patients with neuroblastoma.

This study highlights the importance of targeted NGS combined with FISH and clinicopathological analysis for accurate diagnosis in NTRK fusion PTC. While pan-TRK IHC is useful for initial screening, confirmatory NGS is essential to avoid false-negative results.

P1, N=160, Recruiting, SystImmune Inc. | N=120 --> 160

The Pan Lung Cancer PCR Panel was highly concordant with other assays. The panel can be performed in local laboratories with a rapid turnaround time and represents an attractive alternative to next-generation sequencing for patients with lung cancer.

Owing to the presence of neural tissue, NTRKs are highly positive in IHC, making these genes unsuitable as biomarkers for assessing NTRK inhibitor sensitivity and resistance, which are tissue-agnostic drugs. The observed low fusion rate is consistent with the literature, and the significance of the numerous point mutations identified as agnostic markers warrants further investigation. NTRK expression, fusion, and point mutations were not associated with clinical parameters or survival.

While first-generation TRK kinase inhibitors, such as entrectinib and larotrectinib, have shown positive responses in TRK fusion-positive cancers, resistance mutations against these inhibitors in the kinase domain limit their efficacy...By conjugating entrectinib to thalidomide, we identified JWJ-01-378 as a potent and selective cereblon (CRBN)-recruiting degrader of the TPM3-TRKA fusion...TPM3-TRKA degradation by JWJ-01-378 suppressed downstream signaling and reduced cancer cell viability, with improved responses compared to a heterobifunctional control compound that cannot degrade TPM3-TRKA. Together, our study expands the toolbox of selective compounds for evaluating targeted degradation of TRK fusions in diseases including cancer.

While these practices have become more commonplace, unified guidelines have yet to be established. In this review of the literature, we evaluate the advantages and pitfalls of sequential biomarker testing during disease progression in patients with mCRC.