Neurofibrosarcoma (MPNST)

A malignant tumor that arises from small cutaneous nerves, is locally aggressive, and has a potential for metastasis. Characteristic histopathologic features include proliferating atypical spindle cells with slender wavy and pointed nuclei, hypocellular areas, and areas featuring organized whorls of fibroblastic proliferation. The most common primary sites are the extremities, retroperitoneum, and trunk. These tumors tend to present in childhood, often in association with NEUROFIBROMATOSIS 1. (From DeVita et al., Cancer: Principles & Practice of Oncology, 5th ed, p1662; Mayo Clin Proc 1990 Feb;65(2):164-72)

Also Known As:

Networked: 1040 relevant articles (55 outcomes, 132 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Neoplasms (Cancer)
2.	Neurofibrosarcoma (MPNST)
3.	Neurilemmoma (Schwannoma)
4.	Sarcoma (Soft Tissue Sarcoma)
5.	Neurofibromatosis 1 (Neurofibromatosis Type I)

Experts

1.	Ratner, Nancy: 27 articles (01/2022 - 01/2005)
2.	Carroll, Steven L: 25 articles (01/2021 - 08/2003)
3.	Gutmann, David H: 18 articles (07/2020 - 03/2002)
4.	Lazar, Alexander J: 17 articles (01/2022 - 05/2009)
5.	Hirbe, Angela C: 14 articles (10/2021 - 08/2013)
6.	Kluwe, Lan: 14 articles (07/2020 - 05/2004)
7.	Perry, Arie: 14 articles (01/2020 - 02/2004)
8.	Roth, Kevin A: 12 articles (10/2019 - 08/2003)
9.	Lev, Dina: 12 articles (01/2018 - 05/2009)
10.	Cripe, Timothy P: 12 articles (10/2017 - 06/2006)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Neurofibrosarcoma:

1.	Mitogen-Activated Protein Kinase Kinases (MEKs)IBA 01/01/2021 - "Finally, a combination of MEK and MET inhibition demonstrated activity in models of MPNST and may therefore be effective in patients with MPNST harboring genetic alterations in NF1. " 12/01/2020 - "Combined Inhibition of SHP2 and MEK Is Effective in Models of NF1-Deficient Malignant Peripheral Nerve Sheath Tumors." 01/01/2022 - "However, the efficacy of MEK inhibitor (MEKi) monotherapy was limited in MPNST and the relative mechanisms remained largely unexplored. " 02/12/2021 - "Efficacy of MEK inhibition in a recurrent malignant peripheral nerve sheath tumor." 01/01/2023 - "Antitumor activity of CDK4/6 and MEK inhibitors was measured in MPNST cell lines, patient-derived xenografts (PDX), and de novo mouse MPNSTs, with the latter used to determine anti-PD-L1 response. "
2.	Proteins (Proteins, Gene)FDA Link 12/17/2013 - "High expression of EGFR protein was associated with poor disease-free and overall survival of human MPNST patients. " 01/01/2022 - "In this study, a comprehensive proteomic analysis of the proteins secreted by the sNF96.2 human SC line, derived from a patient with MPNST, was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). " 05/03/2019 - "This study aimed to examine the function of High mobility group protein A2 (HMGA2) in NF1 MPNST progression and the underlying molecular mechanism. " 07/01/2023 - "In NF1-associated PNST, expression of proteins involved in Ras-signaling and development is upregulated not only in MPNST, but also in benign PNF with the potential for malignant dedifferentiation. " 07/01/2023 - "All proteins examined showed highest expression levels/highest frequency of expression in MPNST. "
3.	Doxorubicin (Adriamycin)FDA LinkGeneric 01/01/2020 - "The CP-Dox formulation was superior to free doxorubicin in MPNST models. " 02/01/2013 - "We also discovered that the increased Bcl-xL expression caused an increase in drug resistance to doxorubicin in MPNST-derived SCs. " 01/01/2018 - "Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors." 01/01/1993 - "The in vivo development of radiation- and doxorubicin-induced resistance was studied in a chemosensitive and radiosensitive human neurogenic sarcoma (Essen neuroectodermal tumor line 2) xenografted in nude mice. " 09/17/2013 - "Despite TOP2A overexpression in these tumors, doxorubicin resistance is common, and the mechanisms of chemotherapy resistance in MPNST are poorly understood. "
4.	Imatinib Mesylate (Gleevec)FDA Link 05/04/2013 - "The results suggest that imatinib mesylate may be useful in the treatment of MPNST patients and in vitro studies may help select cells that are sensitive to imatinib mesylate in vivo." 04/01/2014 - "Our data showed that the imatinib-mediated autophagy can function as a cytotoxic mechanism and that appropriate modulation of autophagy may sensitize MPNST cells to imatinib, which in turn may be a novel therapeutic strategy for MPNST. " 04/01/2014 - "We found that the treatment of MPNST cell lines with imatinib induced autophagy. " 04/01/2014 - "Therefore, cellular reactions of imatinib were investigated in vitro using 3 MPNST cell lines. " 04/01/2014 - "Appropriate modulation of autophagy sensitizes malignant peripheral nerve sheath tumor cells to treatment with imatinib mesylate."
5.	S100 Proteins (S 100 Protein)IBA 02/01/2014 - "The findings in this study indicate that GAP43 is expressed in malignant peripheral nerve sheath tumors (n=18/21; 86%) and demonstrates a sensitivity superior to S100 protein (n=13/21; 62%). " 06/01/2022 - "Currently, strong and diffuse immunostaining for S100 protein and SOX10 is generally regarded as a characteristic feature of epithelioid MPNST. " 01/01/2016 - "Loss of H3K27me3 is highly specific for malignant peripheral nerve sheath tumor (although only modestly more sensitive than S-100 protein and SOX10) and may be a useful diagnostic marker. " 08/01/2013 - "The lesion was unique in that it manifested malignant change in the S-100 protein-positive component, which was classified as malignant peripheral nerve sheath tumor. " 12/01/2009 - "Malignant peripheral nerve sheath tumor of the uterine cervix expressing both S-100 protein and HMB-45."
6.	TamoxifenFDA LinkGeneric 01/01/2011 - "Tamoxifen was also effective in vivo, demonstrating potent antitumor activity in mice orthotopically xenografted with human MPNST cells. " 01/01/2011 - "Further, ablation of ERβ and GPER had no effect on MPNST proliferation, survival, or tamoxifen sensitivity, indicating that tamoxifen acts via an ER-independent mechanism. " 01/01/2011 - "To test this hypothesis, we examined tamoxifen effects on MPNST cell proliferation and survival, MPNST xenograft growth, and the mechanism by which tamoxifen impeded these processes. " 01/01/2011 - "Tamoxifen inhibits malignant peripheral nerve sheath tumor growth in an estrogen receptor-independent manner." 11/01/2014 - "These findings suggest that combinatorial therapy with tamoxifen and trifluoperazine is effective against MPNSTs because these agents target complementary pathways that are essential for MPNST pathogenesis. "
7.	Messenger RNA (mRNA)IBA 05/01/2004 - "This study represents a comprehensive gene-expression analysis of an MPNST-derived cell line and the first comprehensive global mRNA profile of nhSCs in culture. " 01/01/2017 - "Our results indicated that in MPNST samples BRD4 mRNA levels were not upregulated and that MPNST cell lines were relatively insensitive to the bromodomain inhibitor JQ1. " 02/01/2016 - "RT-MSP and RT-PCR data showed low methylation levels and detectable mRNA expression of MAGEB2, respectively, in one MPNST cell line, but high methylation level and absence of expression in each other cell line and in normal cells. " 01/21/2010 - "EYA4 mRNA was elevated more than 100-fold as estimated by quantitative real-time PCR in most MPNST cell lines. " 10/01/2001 - "All of the neoplastic lesions of nerve sheath showed a consistent but variant expression of BMP-2, 3, 4, and 5. The expression signals of BMP-2, 3, 5 mRNA in malignant schwannoma were relatively lower than in benign lesions except for the expression of BMP-4 mRNA. "
8.	Sirolimus (Rapamycin)FDA Link 01/01/2012 - "To determine the significance of Pten status for treatment with the mTOR inhibitor rapamycin we treated 5 MPNST cell lines with rapamycin. " 05/01/2009 - "MPNST cells were sensitive to rapamycin; however, rapamycin enhanced pAKT and peIF4E expression. " 06/14/2016 - "A higher cytotoxic effect was observed with AZD8055 compared to rapamycin in the NF1-null MPNST-derived cell lines with IC50 ranging from 70 to 140 nM and antiproliferative effect was confirmed in PNF-derived Schwann cells. " 09/19/2014 - "Moreover, combinational use of artesunate and rapamycin enhanced the cytotoxic effect on MPNST cells. " 10/15/2021 - "A Phase I Study of the Combination of Pexidartinib and Sirolimus to Target Tumor-Associated Macrophages in Unresectable Sarcoma and Malignant Peripheral Nerve Sheath Tumors."
9.	Sorafenib (BAY 43-9006)FDA Link 06/01/2008 - "Metastatic chest wall malignant schwannoma responding to sorafenib: case report and literature review." 12/01/2013 - "A patient with sporadic metastatic MPNST and the BRAF V600E mutation was treated with standard doses of sorafenib and later vemurafenib and followed for response. " 06/01/2008 - "We present a case of a major clinical response to the tyrosine kinase inhibitor (TKI) sorafenib in a patient with metastatic MPNST. " 04/01/2008 - "With growth inhibition at the low nanomolar range, sorafenib, by inhibiting the mitogen-activated protein kinase pathway, may prove to be a novel therapy for patients with MPNST." 01/01/2019 - "A Phase II Trial of Sorafenib and Dacarbazine for Leiomyosarcoma, Synovial Sarcoma, and Malignant Peripheral Nerve Sheath Tumors."
10.	trametinibIBA 01/01/2023 - "Here we present a case of a patient diagnosed with sporadic MPNST with an identified NF1 gene treated successfully with trametinib." 12/01/2020 - "Trametinib decreased pERK expression in MPNST xenografts but did not prolong survival or decrease Ki67 expression. " 12/01/2020 - "We conducted preclinical pharmacokinetic (PK) and pharmacodynamic studies of two MEK inhibitors, trametinib and selumetinib, in two MPNST models and analyzed tumors for intratumor drug levels. " 01/01/2017 - "Taken together, our study suggests a model in which overexpression of wild-type PDGFRA associated with NF1 deficiency leads to aberrant activation of downstream RAS signaling and thus contributes importantly to MPNST development-a prediction supported by the ability of the kinase inhibitor sunitinib alone and in combination with the MEK inhibitor trametinib to retard MPNST progression in transgenic fish overexpressing the wild-type receptor."

Therapies and Procedures

1.	Therapeutics 09/01/2019 - "Patients with PD-L1-positive, metastatic MPNST may be candidates for immune-checkpoint therapy, which may produce a durable complete remission. " 01/01/2016 - "Unfortunately, current treatment modalities for MPNST are limited, with no targeted therapies available and poor efficacy of conventional radiation and chemotherapeutic regimens. " 11/02/2023 - "To address the critical need for novel therapeutics in MPNST, we aimed to establish an ex vivo 3D platform that accurately captured the genomic diversity of MPNST and could be utilized in a medium-throughput manner for drug screening studies to be validated in vivo using patient-derived xenografts (PDX). " 01/01/2023 - "Sixty-four patients (29 male, 35 female, median age 39 years (range 15-81)) with MPNST were enrolled on 1 of 5 trials of single agent or combination therapy that were determined to be inactive. " 02/12/2021 - "Similarly, trials of therapies targeting MPNST genomic drivers have thus far been unsuccessful. "
2.	Drug Therapy (Chemotherapy) 11/01/2003 - "Although chemotherapy is generally ineffective in most cases of malignant schwannoma, we did experience some positive results with the IVA2 protocol. " 11/01/2017 - "Because of the rarity of intrathoracic MPNST, the optimal method of diagnosis and the efficacy of chemotherapy are unknown. " 01/28/2023 - "Perioperative chemotherapy had limited efficacy for disease-specific overall survival in patients with localized malignant peripheral nerve sheath tumors." 01/01/2023 - "The prognosis of malignant schwannoma is usually poor, characterized by a rapidly progressive disease course and a poor response to chemotherapy. " 12/01/2020 - "MPNST is usually associated with poor prognosis, mostly due to their aggressive behavior, high metastatic potential, and resistance to chemotherapy. "
3.	Radiotherapy 01/01/2020 - "Complete resection and adjuvant X-ray radiotherapy would be an effective treatment for MPNST of the cervical spine, even if en bloc resection with a wide margin is impossible. " 01/01/2006 - "Postoperative radiation therapy for MPNST has led to a significant reduction in local recurrence. " 12/01/1994 - "Radical surgery and radiation therapy are effective for treating intracranial malignant schwannoma. " 07/01/2014 - "Surgery is associated with improved survival, whereas radiation therapy is associated with decreased survival in this cohort with malignant peripheral nerve sheath tumor in the spine. " 01/01/2018 - "The purpose of this study is to investigate local control (LC), survival outcomes, and associated prognostic factors for patients with malignant peripheral nerve sheath tumors (MPNSTs) treated with combined surgery and radiation therapy (RT). "
4.	Neoadjuvant Therapy 01/01/2019 - "Pathologic Response to Neoadjuvant Therapy is Associated With Improved Long-term Survival in High-risk Primary Localized Malignant Peripheral Nerve Sheath Tumors." 11/01/2022 - "A 20.5 cm Malignant Peripheral Nerve Sheath Tumor of the Anterior Mediastinum Showing Response to Neoadjuvant Therapy." 01/01/2020 - "We previously reported a case of MPNST involving the penis in a 14-month-old boy treated with neoadjuvant chemotherapy, total penectomy, and adjuvant radiation. " 01/01/2017 - "We performed a retrospective analysis of the patients at our institution with a biopsy-proven diagnosis of MPNST that underwent neoadjuvant chemotherapy prior to surgery. " 01/01/2019 - "Although the impact of neoadjuvant chemotherapy on the outcome of primary localized MPNST patients continues to be debated, this study shows that a pathologic response to therapy is associated with a significant improvement in DSS. "
5.	Photochemotherapy (Photodynamic Therapy) 04/02/2020 - "A Novel Treatment Modality for Malignant Peripheral Nerve Sheath Tumor Using a Dual-Effect Liposome to Combine Photodynamic Therapy and Chemotherapy." 01/01/2017 - "Doxycycline potentiates antitumor effect of 5-aminolevulinic acid-mediated photodynamic therapy in malignant peripheral nerve sheath tumor cells." 04/02/2020 - "In this study, we investigated the possibility of combining photodynamic therapy (PDT) and chemotherapy to treat MPNST by using a dual-effect liposome (named as PL-cDDP-Ce6), in which a chemotherapeutic agent, cisplatin (cDDP), and photosensitizer, chlorine e6 (Ce6) were encapsulated in the same carrier. "