Despite an initial 13 kg weight gain over 9 months, split between fat and lean mass, subsequent fat loss (~3.5 kg) occurred while lean mass was preserved. This case suggests that prolonged, structured exercise is a safe and feasible strategy to attenuate entrectinib-associated metabolic effects and support physical function during targeted therapy in advanced NSCLC.

This analysis demonstrates continued efficacy of entrectinib in Asian patients with advanced ROS1-fp NSCLC, both overall and in the 1L setting. No new safety signals emerged.

Although NTRK-associated fusions are significant in various cancers and have led to the development of targeted therapies, such as larotrectinib and entrectinib, the specific molecular impact of atypical PRUNE2::NTRK2 fusion remains unclear. The PRUNE2::NTRK2 gene fusions described here express a non-functional TrkB protein, and it is unclear whether the PRUNE2 function is intact or affected.

This case report identifies a novel SNX25-ROS1 fusion mutation in NSCLC, showing strong sensitivity to ROS1-targeted therapy. It highlights the importance of molecular profiling in detecting rare genetic alterations and underscores the therapeutic potential of targeted treatments for NSCLC with unique molecular subtypes.

Our study reveals a novel mechanism by which the NOTCH2-NTRK1 fusion confers resistance to osimertinib through its interaction with EGFR in NSCLC.

Importantly, we identified ROS1 p.K1991N as a potential acquired drug resistance mutation to crizotinib, suggesting that entrectinib may serve as a targeted therapy to overcome this resistance mechanism. ROS1 rearrangement could potentially represent a novel driver mutation in MPM, especially in female adults. This case report illustrates the benefits of molecular detection in MPM and underscores the potential for lessons learned from other solid tumors to inform treatment strategies for rare diseases.

The GSEA and DOEA showed that NTRK signalling was enriched for kinase inhibitors responses, representing evidence that NTRK1/2/3 expression may serve as biomarkers for multiple kinase inhibitors, including entrectinib-the tissue-agnostic kinase inhibitor for cancers with NTRK gene fusions. The results demonstrated that fusion-negative NTRK signalling may be active in CRC and may contribute to the molecular pathogenesis and biology of the disease. The results also demonstrated that the NTRK1/2/3 expression may be predictive multiple kinase inhibitors.

Drug sensitivity assays revealed an IC₅₀ of 64.0 nM for entrectinib and 806.8 nM for osimertinib, indicating reduced sensitivity to EGFR inhibition. We provided experimental evidence for that TPM3-NTRK1 fusions can mediate acquired resistance to osimertinib in a new lung adenocarcinoma cell line. LUNK1 represents a useful preclinical model for investigating resistance mechanisms and assessing dual-targeted treatment strategies.

This case highlights a potentially fatal early-phase cardiac complication of entrectinib and supports the use of early electrocardiographic monitoring and therapeutic plasma exchange as management and rescue strategies.

This case highlights acquired MTAP loss during disease progression in ROS1-rearranged NSCLC. Despite persistent CD74-ROS1 fusion and absence of known resistance mutations, the patient developed CNS progression after entrectinib, underscoring the value of longitudinal genomic profiling in guiding treatment decisions.

P1, N=13, Active, not recruiting, OHSU Knight Cancer Institute | Suspended --> Active, not recruiting

Specifically, we found that tanshinone IIA could mitigate the cardiotoxic effects of entrectinib by reducing HMGB1 protein levels. Taken together, our findings elucidated the mechanism underlying entrectinib-induced cardiotoxicity, offering a theoretical foundation for the safer clinical application of this targeted therapy.