NTRK positive

The patient remains disease-free at 9 months postoperatively. This case highlights the importance of comprehensive molecular testing in ALK-negative IMT and demonstrates that complete surgical resection can achieve excellent outcomes even in rapidly growing lesions.

First-generation tyrosine kinase inhibitors (TKIs) such as crizotinib displayed significant early reactions but faced challenges due to restricted central nervous system (CNS) penetration and mutation resistance, while entrectinib and larotrectinib expanded treatment options but also experienced resistance...Safety data shows an acceptable toxicity profile, mainly featuring gastrointestinal and hepatic adverse effects, with fewer neurocognitive side effects compared to lorlatinib...Current trials and regulatory activities in China, the U.S., and other locations demonstrate taletrectinib's growing clinical significance. Taletrectinib's well-rounded pharmacological attributes of systemic action, intracranial effectiveness, resistance range, and tolerability render it an intriguing enhancement to the framework of precision oncology.

Dabrafenib plus trametinib has shown superiority over chemotherapy in pediatric low-grade gliomas and activity against high-grade diseases. Larotrectinib and entrectinib provide tumor-agnostic options for NTRK-fusion-positive tumors with central nervous system penetration. Selumetinib offers clinical benefits in NF1-associated plexiform neurofibromas and shows promise for treating NF1-related low-grade gliomas. Tovorafenib, a type II RAF inhibitor active in BRAF-altered tumors (including BRAFKIAA1549 fusion), achieved robust responses, thereby leading to FDA approval. ONC201 (dordaviprone) has received accelerated approval for the treatment of H3 K27M-mutant diffuse midline gliomas, with Japanese trials and patient-initiated programs expanding access. Abemaciclib, a CDK4/6 inhibitor, is under phase II evaluation for pediatric high-grade glioma and diffuse midline glioma, including sites in Japan. Neurosurgeons play a pivotal role in securing high-quality biopsies, thus enabling comprehensive molecular diagnostics and facilitating enrollment in international trials. This review summarizes current targeted therapies and ongoing studies and outlines practical considerations for integrating precision oncology into pediatric neuro-oncology in Japan.

In children with NTRK fusion-positive sarcomas, upfront TRK inhibition yielded faster, deeper responses and eliminated mutilating surgery in our cohort. These data support TRK inhibitors as preferred neoadjuvant options, particularly to facilitate non-morbid resections and to avoid functional disability.

Further in vivo assay displayed that 20 effectively inhibited tumor growth with no apparent toxicity in the Ba/F3-LMNA-NTRK1G667C xenograft model. Overall, these findings indicated that, unlike conventional inhibitors, such bifunctional agents represent the first class of monovalent small molecules capable of effectively degrading TRK xDFG mutants, providing valuable insights into overcoming TRK xDFG-mediated clinical resistance.

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.

Recognition of LG-TNBCs is essential to prevent overtreatment and guide personalized patient management. Molecular characterization provides diagnostic confirmation and therapeutic opportunities, particularly for NTRK-fusion-positive tumors treatable with targeted inhibitors, highlighting the importance of precision medicine in rare breast tumors.

The patient remains stable with no evidence of local, nodal, or metastatic disease for more than three years following the initial presentation. This report aims to propose the use of larotrectinib as a management option for recurrent NTRK-positive cervical sarcomas.

Ultra-rare GMN-TDGAs included a PTCH1::GLI1-positive renal epithelioid mesenchymal neoplasm, a BRAF-deleted renal spindle cell tumor, and a MYOD1-mutated prostatic spindle cell rhabdomyosarcoma. Conclusively, molecular profiling highlights the histologic and genetic diversity of GMNs, supporting challenging diagnoses and informing personalized therapies.

This case underscores a critical dissociation between oncologic response and vascular complications, indicating that tropomyosin receptor kinase (TRK) inhibitor monotherapy may be insufficient to prevent PTTM. Comprehensive management may require concurrent strategies targeting the pulmonary microvasculature, including antiangiogenic therapy and modulation of cytokine and growth factor signaling.

This novel finding opens the window for the use of tropomyosin receptor kinase (TRK) inhibitor therapy in these subtypes of GIST. In this case report, we present a rare NTRK3 fusion gastrointestinal stromal tumor (GIST) in a female patient with significant response to entrectinib...After neoadjuvant imatinib therapy (400 mg/day), partial response was achieved with tumor shrinkage to 14.1cm×7.6cm×15.5cm, followed by radical surgery...The patient maintained sustained response without adverse events during final follow-up. This case highlights the breakthrough efficacy of TRK inhibitors in treating NTRK-fusion GIST and confirms the critical value of liquid biopsy in monitoring drug resistance mechanisms and guiding precision treatment.

This work highlighted the importance of selecting appropriate exposure measures in exposure-response analyses, particularly when dose or dose frequencies change throughout treatment. The integrated exposure-response analyses provided a robust framework to support the repotrectinib dosing strategy.