NF1 (Neurofibromin 1)

This work provides the first genomic characterisation of a diagnosed MDS cohort in China and establishes the first risk prediction model for MDS-to-AML transformation, alongside novel prognostic models for OS and PFS. These tools offer improved prognostic prediction and potential guidance for therapeutic strategies in Chinese patients with MDS.

The cooperative GOG 281/LOGS trial showed that trametinib, an MEK inhibitor (MEKi), was significantly more effective than standard-of-care options (including chemotherapy or hormonal therapy) in increasing progression-free survival (median PFS 13.0 months vs. 7.2 months; hazard ratio 0.48, p < 0.001)...Genomic and multi-omic profiling have revealed actionable vulnerabilities and precision oncology approaches. The advent of biomarker-directed trials, molecular subtyping incorporation, and innovative computational strategies is likely to gradually ameliorate therapy selection and, thereby, finally improve long-term outcomes for patients with this complex disease.

The development of new agents for MPNST treatment has shifted away from solely targeting RAS pathway gene products to stimulating the immune system and manipulating other MPNST driver mutations such as CDKN2A/B, SUZ12, EED, and TP53. This review presents recent advances in the treatment of sarcomas and the future of drug development targeting MPNSTs.

Novel therapeutic strategies, including AAV-based gene therapy aimed at restoring NF1 function, oncolytic herpes simplex virus (oHSV) therapy targeting RAS-dysregulated tumor cells, and chimeric antigen receptor T cell (CAR-T) therapy targeting NF1-associated tumors, are under active investigation. In this review, we explore the genetic mechanisms underlying NF1 and highlight recent advances in therapeutic development with a special focus on AAV-based gene therapies alongside other approaches with recent clinical and translational advancements.

The study provides a TT-focused prospective analysis still rare in pediatric oncology. The outcomes indicate satisfactory tolerance and promising efficacy of TT, prompting an update of current treatment standards for several pediatric cancers.

Our findings highlight the value of optimized WES strategies in improving diagnostic accuracy and yield, particularly for pediatric patients with atypical clinical presentations. This study represents one of the most comprehensive assessments of NF1 molecular diagnostics in a Chinese pediatric population.

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.

Awareness of rare diseases such as NF1 is essential in critical care settings. Patients presenting with café-au-lait spots or cutaneous neurofibromas are at risk of vascular complications due to vascular fragility. This case of dual bleeding sources and airway obstruction from a neck hematoma underscores the need for interdisciplinary management. The role of proactive vascular screening in critically ill NF1 patients remains uncertain. Future approaches may incorporate advanced imaging and biomarker development to better stratify vascular risk and guide individualized care.

This case underscores critical clinical insights: NF1-associated giant lateral thoracic meningoceles may manifest respiratory symptoms alongside severe complications, including rupture and IHS. Crucially, procedures such as thoracentesis require extreme caution, as they risk exacerbating CSF leakage and may precipitate life-threatening cerebellar tonsillar herniation.

These findings underscore the importance of asparaginase phenotype-related SNP, ADSL (793-49A > C), in personalized treatment strategies based on genetic profiling and clinical parameters, potentially enhancing therapeutic efficacy and patient outcomes in pediatric BCP-ALL.

Driver alterations in the RAS-MAPK signaling pathway confer radioresistance in metastatic NSCLC. These genetic alterations may serve as biomarkers to personalize RT strategies or as targets to enhance radiosensitivity.

Further adult studies are necessary to elucidate population differences and understand varied symptom onset across age. Collaborative efforts in diagnosis and management are crucial for optimising care in NF1 patients with OPGs.