Neurofibrosarcoma

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.

This case underscores the importance of recognizing distinct features of malignant extrarenal rhabdoid tumor to ensure accurate diagnosis and early intervention, as the disease remains aggressive with a high risk of recurrence despite multimodal therapy.

While degenerative changes within neurofibromas are typically benign, they may obscure early malignant transformation, complicating diagnosis. These findings underscore the need for continued surveillance of recurrent neurofibromas and further research into MPNST pathogenesis in non-NF1 populations.

The identification of patients with NF1 and their interittent follow-up are important for the early detection of potential complications, especially tumorigenesis. This review aimed to summarize NF1-associated tumors in pediatric patients and recently developed targeted therapies for treating these tumors.

RECQL4 knockdown in glioma and MPNST cell lines resulted in increased apoptosis and susceptibility to ATR-inhibitors. Our findings show that RECQL4 expression has divergent patterns across tumor types and that targeting RECQL4 may dampen tumor survival and enhance susceptibility to ATR inhibitor therapy in CNS tumors.

We described the clinical features, treatment, and clinical outcomes of 5 cases of MPNST, including one case of MPNST with NF1 gene mutation. This provides valuable clinical experience for the treatment of this rare tumor.

Pulmonary sarcomatoid carcinoma requires immediate and optimal therapeutic intervention because of its aggressive nature and narrow therapeutic window. In health care systems with limited access to immunotherapy, emphasis must be placed on achieving complete surgical resection and intensive postoperative surveillance. This case highlights the need for health care policy discussions regarding expanded access to immunotherapy for patients with favourable biomarker profiles, as current restrictions may significantly impact outcomes in this devastating disease.

We present a novel genetically engineered mouse model that faithfully recapitulates human PRC2-loss MPNST, enabling mechanistic and preclinical studies of malignant transformation in the context of PRC2 loss.

P1, N=44, Active, not recruiting, Seattle Children's Hospital | Recruiting --> Active, not recruiting | Trial primary completion date: Jun 2025 --> Jun 2040

Among 82 participants, the assay achieved an AUC of 0.904, compared with 0.735 for genome‑wide CNAs. We also detected recurrent disease‑specific driver alterations, relapse up to three months before diagnosis, and early clearance consistent with durable remission.

The choice of tissue used for analytical validation is important and warrants further evaluation and guidance. Establishing an optimal balance between analytical sensitivity and analytical specificity during protocol optimization is key.