NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)

P1/2, N=67, Recruiting, D3 Bio (Wuxi) Co., Ltd | Active, not recruiting --> Recruiting | Trial completion date: Apr 2028 --> Aug 2028 | Trial primary completion date: Apr 2028 --> Aug 2028

Knockdown of NTRK1, which encodes TrkA, reduced cell viability and sensitized ATC cells to paclitaxel. Entrectinib was well tolerated at the administered dose, with no significant changes in body weight and serum biochemical markers. Collectively, these findings identify TrkA as a potential therapeutic target in ATC and support further investigation of entrectinib-based combination strategies to improve ATC treatment outcomes.

Continuous genomic monitoring is essential for identifying resistance mechanisms and guiding precision therapy. Future studies should explore the impact of different fusion partners on tumor behavior and therapeutic response.

RAF/BRAF-driven mesenchymal tumours possess a broader clinicopathologic spectrum than traditionally recognised, frequently affecting adults and deep/visceral sites. Their inherently variable immunophenotypes and the presence of high-grade morphologic features do not strictly predict an aggressive clinical trajectory. Comprehensive molecular profiling is essential to refine diagnostic criteria, accurately identify these neoplasms, and elucidate the genomic events associated with tumour progression.

Our results support the incorporation of ALK immunohistochemistry as a screening tool and demonstrate the utility of anchored multiplex PCR-based RNA sequencing for the detection of therapeutically relevant fusions, particularly those with uncommon partners. This integrated approach may refine the diagnosis and support consideration of ALK-directed therapy in these rare tumors.

We present a case of 54-year-old non-smoking woman with a history of uterine fibroids (total hysterectomy in 2008) and depression (on mirtazapine)...She received two cycles of neoadjuvant chemotherapy (carboplatin 577 mg + paclitaxel 259 mg), achieving a partial response (PR)...In patients with a history of lung cancer presenting with a vaginal mass, the possibility of vaginal metastasis from lung cancer should be carefully evaluated and advanced diagnostic methods such as NGS are recommended. This case highlights the advantages of comprehensive NGS followed by chemotherapy and osimertinib in managing NSCLC with vaginal metastasis and EGFR/NTRK1 co-mutations.

In CRC, TAT was 4.1, 5.3, and 10.2; QNS 0%, 0%, 7.5%; detection 63.9%, 62.5%, and 57.1%. OPA provides faster TAT and lower QNS rates with comparable detection of actionable alterations, supporting its use for community-based molecular testing in NSCLC and CRC.

P2, N=534, Active, not recruiting, Hoffmann-La Roche | Trial completion date: May 2026 --> Jun 2027 | Trial primary completion date: May 2026 --> Jun 2027

In this cohort, the DNA+RNA-based panel showed a higher detection rate for TK fusions, although the panels were applied to different patient groups and the sensitivity and specificity could not be determined. Future studies evaluating different test types on the same tumor specimens are warranted to clarify whether the dual-sequencing approaches can improve the identification of actionable genetic events.

Baseline adrenal metastasis serves as a poor prognostic indicator. Distinct genomic mutation signatures are associated with clinical characteristics, suggesting potential pathways for personalized treatment strategies.

FISH may represent a useful intermediate diagnostic tool when NGS is unavailable but requires cautious interpretation particularly in cases with atypical or isolated signals. NGS-based molecular confirmation remains essential for the definitive identification of NTRK fusions.

P=N/A, N=10, Not yet recruiting, Bristol-Myers Squibb