^
10d
Primary intracranial DICER1-mutant sarcoma: a clinicopathological analysis of seven cases (PubMed, Zhonghua Bing Li Xue Za Zhi)
Primary intracranial DICER1-mutant sarcoma is a rare tumor. Understanding its morphological characteristics, immunohistochemical and molecular markers and differential diagnosis is crucial to avoid misdiagnosis and to improve diagnostic accuracy of this tumor.
Retrospective data • Journal
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TP53 (Tumor protein P53) • ATRX (ATRX Chromatin Remodeler) • DICER1 (Dicer 1 Ribonuclease III) • SALL4 (Spalt Like Transcription Factor 4)
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TP53 mutation
16d
Multiomic analyses reveal new targets of polycomb repressor complex 2 in Schwann lineage cells and malignant peripheral nerve sheath tumors. (PubMed, Neurooncol Adv)
Our findings support the Notch pathway as a druggable target in MPNSTs. Our identification of PRC2-regulated genes and pathways could result in more novel therapeutic approaches.
Journal
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NF1 (Neurofibromin 1) • SUZ12 (SUZ12 Polycomb Repressive Complex 2 Subunit)
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Ogsiveo (nirogacestat)
19d
Fatal abdominal hemorrhage following surgery to remove a retroperitoneal MPNST associated with NF1: A case report. (PubMed, Medicine (Baltimore))
It is crucial to assess the potential for heterogeneous differentiation in MPNST during pathological diagnosis. In the treatment of MPNST with heterogeneous differentiation, particularly in cases with significant tumor bulk, surgeons must anticipate potential hemorrhagic complications and adopt a cautious approach to surgical intervention.
Journal • Surgery
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NF1 (Neurofibromin 1)
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NF1 mutation
21d
Plasma DNA Methylation-Based Biomarkers for MPNST Detection in Patients With Neurofibromatosis Type 1. (PubMed, Mol Carcinog)
Our findings confirmed a unique hypermethylation pattern present during malignant transformation. This study highlights the potential to be investigated further as biomarkers in clinical settings for early MPNST detection in patients with NF1.
Journal • Epigenetic controller
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NF1 (Neurofibromin 1)
21d
Perioperative Observations and Outcome in Surgical Treatment of Malignant Peripheral Nerve Sheath Tumors. (PubMed, Cancers (Basel))
NF1-associated MPNSTs have larger tumor volumes, higher SUVs and MIB-1 proliferation indices, and a shorter overall survival period. Nevertheless, surgery can improve symptoms, particularly medication-resistant pain, and should also be considered in advanced disease for symptom control/improvement.
Journal
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NF1 (Neurofibromin 1)
1m
New P1 trial
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NF1 (Neurofibromin 1)
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mirdametinib (PD-0325901) • Zolinza (vorinostat)
1m
Profiling the cancer-prone microenvironment in a zebrafish model for MPNST. (PubMed, Oncogene)
Finally, we functionally validate a candidate extracellular matrix protein, periostin (POSTN), in human MPNST. This work provides insight into how the microenvironment may regulate MPNST initiation and progression.
Journal
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POSTN (Periostin)
1m
Genomic landscape of superficial malignant peripheral nerve sheath tumor. (PubMed, Lab Invest)
Next-generation sequencing revealed multiple differential features between SF- MPNST, D-MPNST, SCM, and DM, including tumor mutation burden, mutational signatures, and differentially expressed genes. These findings help advance our understanding of disease pathogenesis and improve diagnostic modalities.
Journal • Tumor mutational burden
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TMB (Tumor Mutational Burden) • PRAME (Preferentially Expressed Antigen In Melanoma) • MLPH (Melanophilin) • SOX11 (SRY-Box Transcription Factor 11) • CALB2 (Calbindin 2) • SOX8 (SRY-Box Transcription Factor 8)
1m
Consensus recommendations for an integrated diagnostic approach to peripheral nerve sheath tumors arising in the setting of Neurofibromatosis type 1 (NF1). (PubMed, Neuro Oncol)
We also propose renaming "low-grade MPNST" to "ANNUBP with increased proliferation" to avoid the use of the "malignant" term in this group of tumors with persistent unknown biologic potential. This refined integrated diagnostic approach for NF1-associated peripheral nerve sheath tumors should continue to evolve in concert with our understanding of these neoplasms.
Journal
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TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • SUZ12 (SUZ12 Polycomb Repressive Complex 2 Subunit)
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TP53 mutation
1m
Review • Journal
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NF1 (Neurofibromin 1) • CCND1 (Cyclin D1) • SOX10 (SRY-Box 10) • MME (Membrane Metalloendopeptidase) • MYOD1 (Myogenic Differentiation 1)
1m
Whole-body MRI-based long-term evaluation of pediatric NF1 patients without initial tumor burden with evidence of newly developed peripheral nerve sheath tumors. (PubMed, Orphanet J Rare Dis)
Our results indicate that PN can be newly detected in pediatric patients over time, even if no PN were detected on initial MRI scans. Therefore, it seems reasonable to perform at least a second MRI in pediatric NF1 patients at transition to adulthood, even if they did not display any tumor burden on initial MRI, and when the MRI was performed significantly under the age of 18. With this approach, tumors that may have developed between scans can be detected and patients at risk for complications can be identified.
Journal
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NF1 (Neurofibromin 1)
2ms
TGF-β superfamily-induced transcriptional activation pathways establish the RAD52-dependent ALT machinery during malignant transformation of MPNSTs. (PubMed, Sci Rep)
Telomere elongation achieved by the activation of PAX7 and PAX9 is associated with a poor prognosis. We demonstrated that TGF-β superfamily-induced transcriptional activation pathways activated the RAD52-dependent ALT during malignant transformation of MPNSTs.
Journal
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BRCA2 (Breast cancer 2, early onset) • NF1 (Neurofibromin 1) • TGFB1 (Transforming Growth Factor Beta 1) • RAD52 (RAD52 Homolog DNA Repair Protein) • FEN1 (Flap Structure-Specific Endonuclease 1) • PAX7 (Paired Box 7) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit) • SOX4 (SRY-Box Transcription Factor 4) • BMP2 (Bone Morphogenetic Protein 2) • BMP4 (Bone Morphogenetic Protein 4) • SOX14 (SRY-Box Transcription Factor 14)
2ms
Targeting the Galectin-1/Ras Interaction for Treating Malignant Peripheral Nerve Sheath Tumors. (PubMed, Res Sq)
LLS30 effectively disrupts the Gal-1/Ras interaction, resulting in significant anti-tumor and anti-metastatic effects in MPNST models. These findings indicated that targeting Gal-1 with LLS30 offers a promising therapeutic approach for treating MPNSTs and may also be applicable to other malignancies where Gal-1 and Ras are key oncogenic drivers.
Journal
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KRAS (KRAS proto-oncogene GTPase) • NF1 (Neurofibromin 1) • LGALS1 (Galectin 1)
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KRAS G12V • HRAS G12V
2ms
TSPO deficiency promotes the progression of malignant peripheral sheath tumors by regulating the G2/M phase of the cell cycle via CDK1. (PubMed, Sci Rep)
More importantly, CDK1 knockdown induced significant cell cycle arrest in the G2/M phase. In summary, TSPO deficiency regulates the cell cycle in MPNSTs by targeting CDK1, which may be an effective molecular target for prognosis evaluation and treatment.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • NF1 (Neurofibromin 1) • CASP3 (Caspase 3) • CASP8 (Caspase 8) • CCNA2 (Cyclin A2) • CDK2 (Cyclin-dependent kinase 2) • CDK1 (Cyclin-dependent kinase 1) • CCNB1 (Cyclin B1) • HSPD1 (Heat Shock Protein Family D (Hsp60) Member 1)
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NF1 mutation • CDKN1B expression
2ms
Progress in neurosurgical treatment of neurofibromatosis type 1 (PubMed, Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi)
Preoperative multidisciplinary assessment, intraoperative electrophysiological monitoring, and advanced surgical assistance devices significantly enhance surgical efficacy and safety. Future research should continue to explore new surgical techniques and improve postoperative management strategies to achieve more precise and personalized treatment for NF1 patients.
Review • Journal
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NF1 (Neurofibromin 1)
2ms
Application of multimodal intraoperative neurophysiological monitoring technology in neurofibromatosis type 1 related peripheral nerve tumor surgery (PubMed, Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi)
Multimodal IONM technology can provide real-time detection of nerve provocation and damage. Surgical treatment with multimodal IONM technology is safe and can reduce complications.
Retrospective data • Journal • Surgery
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NF1 (Neurofibromin 1)
2ms
Clinical features and surgical treatments of neurofibromas associated with neurofibromatosis type 1 (PubMed, Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi)
MPNST has the worst prognosis, high incidence of recurrence/metastasis, and short survival period. Total resection combined with radiotherapy can decrease local recurrence.
Retrospective data • Journal
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NF1 (Neurofibromin 1)
2ms
Analysis of clinical features, treatment methods, and prognostic influence factors in patients with malignant peripheral nerve sheath tumor (PubMed, Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi)
FNCLCC grade, R 0 resection, and adjuvant therapies, including radiotherapy and anlotinib-targeted therapy, are closely associated with MPNST prognosis. Complete surgical resection should be prioritized in clinical management, along with adjuvant treatments such as radiotherapy and targeted therapy of anlotinib to improve patient outcomes.
Retrospective data • Journal
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NF1 (Neurofibromin 1)
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Focus V (anlotinib)
2ms
Expression and its clinical significance of cell-cycle dependent kinase 1 in malignant peripheral nerve sheath tumors (PubMed, Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi)
Increased expression of CDK1 is associated with poor prognosis in MPNST patients. Compared to other CDK family members, CDK1 exhibits a unique expression pattern, suggesting its potential as a therapeutic target for MPNST.
Journal
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CDK1 (Cyclin-dependent kinase 1)
2ms
Current state of spinal nerve sheath tumor management and future advances. (PubMed, Neurooncol Adv)
Though surgery is the traditional mainstay of treatment for these tumors, the discovery of the genetic and molecular basis of these diseases in recent decades has prompted investigation into targeted therapies. Here, we give a clinical overview of spinal nerve sheath tumors, their imaging features, current management practices, and explore ongoing advances in systemic therapies.
Review • Journal
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NF2 (Neurofibromin 2)
2ms
Cauda equina malignant peripheral nerve sheath tumor presenting with subarachnoid hemorrhage: a case report. (PubMed, Neurocirugia (Astur : Engl Ed))
On an 8-month follow-up, he had no neurological deficit, with a Karnofsky performance score of 90 points. Surgical evidence of SAH in lumbar spine intradural MPNST is a novel finding.
Journal
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SOX10 (SRY-Box 10)
2ms
The Multimodality Management of Malignant Peripheral Nerve Sheath Tumours. (PubMed, Cancers (Basel))
The aim of multimodality approaches is to optimize both local and systemic control while keeping to a minimum acute and late treatment morbidity. Advances in the understanding of the underlying biology of MPNSTs in both sporadic and NF-1-related contexts are essential for the management and implementation of novel therapeutic approaches.
Review • Journal
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NF1 (Neurofibromin 1)
2ms
Proof of Concept for Genome Profiling of the Neurofibroma/Sarcoma Sequence in Neurofibromatosis Type 1. (PubMed, Int J Mol Sci)
Specifically, the expression changes related to the mutated genes, such as in RBMX, PNPLA6 and AGAP2, were associated with reduced patient survival, distinguishing them as potential prognostic biomarkers. This study underlines the relevance of integrating genomic results with clinical information for early diagnosis and prognostic understanding of tumor aggressiveness.
Journal
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TP53 (Tumor protein P53) • NF1 (Neurofibromin 1) • SUZ12 (SUZ12 Polycomb Repressive Complex 2 Subunit)
2ms
Radiation-Induced Intraosseous Malignant Peripheral Nerve Sheath Tumor: A Case Report. (PubMed, Int J Surg Pathol)
In conclusion, radiation-induced secondary malignancies are a significant late side effect of radiation therapy that can profoundly impact treatment decision-making and requires a high index of suspicion during post radiation surveillance. Malignant peripheral nerve sheath tumor serves as a pertinent example, highlighting the importance of considering long-term risks when developing optimal management plans for cancer patients.
Journal
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SOX10 (SRY-Box 10)
3ms
Neurofibromatosis to neoplasia transition: a rare case report of spindle cell malignant peripheral nerve sheath tumor with literature review. (PubMed, Ann Med Surg (Lond))
This case stands out due to its unique presentation, characterized by a predominantly spindle cell morphology with certain epithelioid features. It is imperative to recognize this condition for an accurate diagnosis, emphasizing the spindle cell-type MPNST and highlighting its exceptionally poor prognosis.
Review • Journal
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TP53 (Tumor protein P53)
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TP53 mutation
3ms
Linking FOXM1 and PD-L1 to CDK4/6-MEK targeted therapy resistance in malignant peripheral nerve sheath tumors. (PubMed, Oncotarget)
Finally, the role of FOXM1 in suppressing anti-tumor immunity and potentially thwarting immune-based therapies is considered. We suggest that future therapeutic strategies targeting the oncogenic network of CDK4/6, MEK, PD-L1, and FOXM1 represent exciting future treatment options for MPNST patients.
Review • Journal
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PD-L1 (Programmed death ligand 1) • NF1 (Neurofibromin 1) • CDK4 (Cyclin-dependent kinase 4) • FOXM1 (Forkhead Box M1)
3ms
Primary Aortic Malignant Peripheral Nerve Sheath Tumor. (PubMed, Vasc Endovascular Surg)
Immunohistochemically, positive S-100 and vimentin; Ki67 levels of 40%; and negative CD34, CK AE1/AE3, and SMA were identified. The aforementioned findings definitively diagnosed primary aortic malignant peripheral nerve sheath tumor, which has been never reported in the literature.
Journal
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CD34 (CD34 molecule) • VIM (Vimentin)
3ms
Case Report: Misdiagnosis of a lipofibromatosis-like neural tumor of the dorsal skin as dermatofibrosarcoma protuberans. (PubMed, Front Surg)
Histological and immunohistochemical detections aid in the differential diagnosis of LPF-NTs. Complete surgical resection is the preferred treatment for LPF-NTs.
Journal
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CD34 (CD34 molecule)
3ms
Cold Atmospheric Plasma Induces Growth Arrest and Apoptosis in Neurofibromatosis Type 1-Associated Peripheral Nerve Sheath Tumor Cells. (PubMed, Biomedicines)
Utilizing established mouse and human cell lines to interrogate the effects of CAP in both in vitro and in vivo settings, we found that NF1-associated PNSTs were highly sensitive to CAP exposure, resulting in cell death. To our knowledge, this is the first application of CAP to NF1-associated PNSTs and provides a unique opportunity to study the complex biology of NF1-associated tumors.
Journal • Tumor cell
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NF1 (Neurofibromin 1)
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NF1 mutation
3ms
MC1372: Vaccine Therapy in Treating Patients with Malignant Peripheral Nerve Sheath Tumor That is Recurrent or Cannot Be Removed by Surgery (clinicaltrials.gov)
P1, N=9, Completed, Mayo Clinic | Recruiting --> Completed | N=30 --> 9 | Trial completion date: Sep 2024 --> Apr 2024 | Trial primary completion date: Sep 2024 --> Apr 2024
Trial completion • Enrollment change • Trial completion date • Trial primary completion date • Surgery
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MV-NIS
3ms
Multi-dimensional immunotyping of human NF1-associated peripheral nerve sheath tumors uncovers tumor-associated macrophages as key drivers of immune evasion in the tumor microenvironment. (PubMed, Clin Cancer Res)
Malignant transformation of NF1-PNST is characterized by an immunosuppressive microenvironment comprising of TAM with high expression of PD-L1, which are associated with inferior outcomes. These findings suggest a clinical potential of immune modulating therapeutics that can unleash an anti-tumor immune response.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • NF1 (Neurofibromin 1) • PD-1 (Programmed cell death 1) • CD163 (CD163 Molecule)
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PD-L1 overexpression • PD-1 overexpression • PD-1 expression
3ms
Interferon-Induced Transmembrane Protein 1 (IFITM1) Is Downregulated in Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors. (PubMed, Int J Mol Sci)
In xenograft mice injected with MPNST cells, IFN-γ treatment successfully suppressed tumor progression with increased IFITM1 expression and decreased Ras and ERK1/2 activation in tumor tissues. Collectively, these results suggest that IFITM1 is closely involved in MPNST pathogenesis and that IFN-γ is a good candidate for the therapeutic treatment of MPNSTs in NF1.
Journal
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NF1 (Neurofibromin 1) • IFNG (Interferon, gamma) • MAPK1 (Mitogen-activated protein kinase 1) • MAPK3 (Mitogen-Activated Protein Kinase 3)
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NF1 mutation • IFNG expression • IFIT1 overexpression • NF1 overexpression
3ms
MEK inhibitors lead to PDGFR pathway upregulation and sensitize tumors to RAF dimer inhibitors in NF1-deficient malignant peripheral nerve sheath tumor (MPNST). (PubMed, Clin Cancer Res)
Our findings suggest that the combination of MEKi and PDGFR and/or RAF dimer inhibitors can overcome MEKi resistance and may serve as a novel targeted therapeutic strategy for NF1-deficient MPNST patients, which in turn could impact future clinical investigations for this patient population.
Journal
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NF1 (Neurofibromin 1) • PDGFRB (Platelet Derived Growth Factor Receptor Beta)
4ms
The CoREST complex is a therapeutic vulnerability in malignant peripheral nerve sheath tumors. (PubMed, bioRxiv)
Transcriptomic analysis of corin-treated MPNST cells demonstrates specific increases in genes associated with axonogenesis and neuronal differentiation as well as altered extracellular matrix; additionally, corin treatment is shown to inhibit MPNST invasion in vitro. These results underscore the critical role of the LHC complex in facilitating MPNST growth and progression and suggest that targeting the LHC complex represents a promising therapeutic approach for this aggressive malignancy.
Journal
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NF1 (Neurofibromin 1) • HDAC1 (Histone Deacetylase 1)
4ms
Donor Stem Cell Transplant After Chemotherapy for the Treatment of Recurrent or Refractory High-Risk Solid Tumors in Pediatric and Adolescent-Young Adults (clinicaltrials.gov)
P2, N=1, Terminated, M.D. Anderson Cancer Center | N=40 --> 1 | Trial completion date: May 2025 --> Aug 2024 | Active, not recruiting --> Terminated | Trial primary completion date: May 2025 --> Aug 2024; PI Request
Enrollment change • Trial completion date • Trial termination • Trial primary completion date
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HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • HLA-B (Major Histocompatibility Complex, Class I, B) • HLA-C (Major Histocompatibility Complex, Class I, C)
|
melphalan
4ms
NSD3::NUTM1 Fusion Sarcoma Mimicking Malignant Peripheral Nerve Sheath Tumor with Prolonged Survival. (PubMed, Biomedicines)
Thus, this case expands NUT fusion sarcomas' histologic and immunohistochemical profile to include mimicking a malignant peripheral nerve sheath tumor (MPNST). Additionally, it indicates that the NSD3::NUTM1 fusion can drive sarcoma genesis.
Journal
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NSD3 (Nuclear Receptor Binding SET Domain Protein 3) • NUTM1 (NUT Midline Carcinoma Family Member 1)
4ms
Imaging findings of type I neurofibromatosis with outcome of malignant peripheral nerve sheath tumor in the right lower extremity. (PubMed, J Clin Ultrasound)
Malignant peripheral nerve sheath tumor (MPNST) is an extremely rare malignancy with neural differentiation potential. The lifetime risk of developing MPNST in NF-1 patients is 8%-13%.
Journal
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NF1 (Neurofibromin 1)
4ms
Immunohistochemical Evaluation of Schlafen 11 (SLFN11) Expression in Cancer in the Search of Biomarker-Informed Treatment Targets: A Study of 127 Entities Represented by 6658 Tumors. (PubMed, Am J Surg Pathol)
Such entities may benefit from alternative treatments or strategies to overcome SLFN11 deficiency-related drug resistance. Our approach and results should serve as a foundation for future biomarker-associated clinical trials.
Journal
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SLFN11 (Schlafen Family Member 11)
4ms
Total Knee Arthroplasty in a Patient With Neurofibromatosis 1. (PubMed, Arthroplast Today)
A primary total knee arthroplasty was performed with a cemented-stemmed hinged knee implant. At 6 months post-surgery, the patient had a dramatic improvement in her pain and quality of life.
Review • Journal
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NF1 (Neurofibromin 1)
4ms
Phase 1/2 Study of MRTX1719 in Solid Tumors With MTAP Deletion (clinicaltrials.gov)
P1/2, N=580, Recruiting, Mirati Therapeutics Inc. | N=370 --> 580
Enrollment change • Metastases
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MTAP (Methylthioadenosine Phosphorylase)
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BMS‐986504