^
    2d
    Driving proteomic imbalance in malignancy provokes proteomic catastrophe and confers tumor suppression. (PubMed, bioRxiv)
    Thus, HSF1 safeguards the cancer proteome to enable the oncogenic potential of mTORC1. This proof-of-principle study highlights provoking proteomic catastrophe as a next-generation therapeutic concept for combating malignancy.
    Journal
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    NF1 (Neurofibromin 1) • TSC2 (TSC complex subunit 2) • HSF1 (Heat Shock Transcription Factor 1) • HSPD1 (Heat Shock Protein Family D (Hsp60) Member 1)
    4d
    Prolonged Mitogen-Activated Protein Kinase Kinase (MEK) Inhibition Induces Increase in Proteolysis and Compensatory Phosphorylation of MEK and Protein Kinase B (AKT) in Plexiform Neurofibroma Cells. (PubMed, Cells)
    FDA-approved mitogen-activated protein kinase kinase (MEK) inhibitors, selumetinib and mirdametinib, have shown ~30% tumor shrinkage in 70% and 42% pNF1 patients, respectively. This response was also observed in MPNST cell lines treated with MEK inhibitors. These findings suggest that adaptive activation of upstream and parallel survival pathways may counteract the intended effects of MEK inhibition and support the rationale for combination strategies to improve therapeutic outcomes in NF1-associated tumors.
    Journal
    |
    NF1 (Neurofibromin 1)
    |
    Koselugo (selumetinib) • Gomekli (mirdametinib)
    4d
    Trametinib and Fimepinostat Induce Malignant Peripheral Nerve Sheath Tumor Cell Death In Vitro. (PubMed, Cancers (Basel))
    These studies demonstrate in vitro efficacy for two candidate MPNST therapeutics which could reduce tumor burden and metastasis in NF1 patients.
    Preclinical • Journal
    |
    NF1 (Neurofibromin 1)
    |
    Mekinist (trametinib) • Koselugo (selumetinib) • Gomekli (mirdametinib) • fimepinostat (CUDC-907)
    6d
    Challenging Limb Salvage in a Crural Malignant Peripheral Nerve Sheath Tumor with Pre-existing Long-Stem Implants: A Case Report. (PubMed, J Orthop Case Rep)
    The unusual longitudinal distribution of the tumor, combined with the constraints imposed by pre-existing long-stem implants, made limb salvage infeasible. Individualized surgical planning, incorporating both oncologic and reconstructive considerations, is essential when managing complex MPNSTs in reconstructively compromised limbs.
    Journal
    |
    SOX10 (SRY-Box 10)
    8d
    Schwannoma: a spectrum from benign to malignant. (PubMed, Rom J Morphol Embryol)
    This study highlights the importance of integrating histopathology and immunohistochemistry for accurate diagnosis and differentiation of peripheral nerve sheath tumors. The recognition of rare variants and analysis of tumor subtypes contribute to a better understanding of these entities, which is crucial for appropriate clinical management.
    Journal
    |
    SOX10 (SRY-Box 10)
    11d
    IFN signaling is associated with radiotherapy response in malignant peripheral nerve sheath tumors. (PubMed, J Clin Invest)
    Analysis of human MPNST resection specimens demonstrated that increased microenvironmental and CD8+ T cell infiltration were associated with improved local control following RT. These results provide a preclinical rationale for combining immunomodulatory agents targeting IFN signaling to improve radiation responses in MPNSTs and potentially other soft tissue sarcomas.
    Journal
    |
    CD8 (cluster of differentiation 8)
    12d
    Immunohistochemistry of melanocytic tumours (PubMed, Pathologie (Heidelb))
    Cases of malignant peripheral nerve sheath tumours are, in contrast to desmoplastic melanoma S‑100 protein negative or express this marker only focally, and show a decreased nuclear expression of H3K27. Desmoplastic melanoma shows a focal nuclear expression of p53 in contrast to neurofibroma.
    Review • Journal
    |
    ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • BAP1 (BRCA1 Associated Protein 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • WT1 (WT1 Transcription Factor) • SOX10 (SRY-Box 10) • CD68 (CD68 Molecule) • PRAME (Preferentially Expressed Antigen In Melanoma) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • MITF (Melanocyte Inducing Transcription Factor) • NES (Nestin) • PRKAR1A (Protein Kinase CAMP-Dependent Type I Regulatory Subunit Alpha)
    13d
    Giant malignant peripheral nerve sheath tumor: Illustrative case and surgical technique. (PubMed, Surg Neurol Int)
    The benefits - including the emotional ones - can be so significant that, despite their malignant lineage, resection and regrowth control remain worthwhile for as long as possible. Four- or six-hand surgery for these tumors can reduce bleeding, operative time, and complications.
    Journal
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    NF1 (Neurofibromin 1)
    13d
    Breathless and Beyond: Anterior Mediastinal Malignant Peripheral Nerve Sheath Tumor as a Rare Neurofibromatosis Type 1 Manifestation. (PubMed, Clin Case Rep)
    Multidisciplinary evaluation, including biopsy and imaging, is essential for diagnosis, with surgical resection as the primary treatment. Early recognition and vigilant monitoring in NF1 patients are crucial for prompt intervention and improved outcomes.
    Journal
    |
    NF1 (Neurofibromin 1)
    14d
    ARST1321: Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Before Surgery in Treating Patients With Newly Diagnosed Non-rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery (clinicaltrials.gov)
    P2/3, N=140, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026
    Trial completion date
    |
    doxorubicin hydrochloride • pazopanib • cyclophosphamide • ifosfamide • daunorubicin
    19d
    Pembrolizumab in advanced malignant peripheral nerve sheath tumors: a single-arm phase 2 trial. (PubMed, NPJ Precis Oncol)
    Mixed response in another patient was associated with PD-L1 expression, and PD-L1 was mostly not co-expressed on CD68+ macrophages or CD8+ cells. The study was prematurely closed due to a slow accrual rate.
    P2 data • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD68 (CD68 Molecule)
    |
    PD-L1 expression
    |
    Keytruda (pembrolizumab)
    19d
    Clinical Outcomes Following Surgical Resection for Patients With Malignant Peripheral Nerve Sheath Tumors. (PubMed, Neurosurgery)
    MPNST are aggressive sarcomas that present challenges in diagnosis and treatment. In our series, NF1-related MPNST patients had the highest OS, likely associated with close monitoring for MPNST among the high-risk NF1-population. Nonextremity tumor locations, recurrent tumors, and postoperative complications were associated with inferior OS and PFS. Multi-institutional studies are warranted to investigate the impact of these prognostic factors in a larger, more heterogeneous MPNST patient cohort and examine the utility of surveillance in the neurofibromatosis patient population under a multidisciplinary team.
    Clinical data • Journal
    |
    NF1 (Neurofibromin 1)