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Malignant peripheral nerve sheath tumor: models, biology, and translation

Oncogene volume 41, pages 2405–2421 (2022)Cite this article

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Abstract

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive, invasive cancer that comprise around 10% of all soft tissue sarcomas and develop in about 8–13% of patients with Neurofibromatosis Type 1. They are associated with poor prognosis and are the leading cause of mortality in NF1 patients. MPNSTs can also develop sporadically or following exposure to radiation. There is currently no effective targeted therapy to treat MPNSTs and surgical removal remains the mainstay treatment. Unfortunately, surgery is not always possible due to the size and location of the tumor, thus, a better understanding of MPNST initiation and development is required to design novel therapeutics. Here, we provide an overview of MPNST biology and genetics, discuss findings regarding the developmental origin of MPNST, and summarize the various model systems employed to study MPNST. Finally, we discuss current management strategies for MPNST, as well as recent developments in translating basic research findings into potential therapies.

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Fig. 1: Morphology and histology of MPNST.
Fig. 2: Key cellular pathways underpinning MPNST development.
Fig. 3: Epigenetic regulation in MPNST.

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Acknowledgements

LQL held a Career Award for Medical Scientists from the Burroughs Wellcome Fund and is the Thomas L. Shield, M.D. endowed Professor in Dermatology. He is supported by funding from the US Department of Defense (NF210010), the National Cancer Institute of the NIH (R01 CA166593), and the Developmental and Hyperactive RAS Tumor SPORE (U54 CA196519); the Neurofibromatosis Therapeutic Acceleration Program; the NF1 Research Consortium Fund; and the Giorgio Foundation.

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  1. Department of Dermatology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 75390-9069, USA

    Bandarigoda N. Somatilaka, Ali Sadek, Renee M. McKay & Lu Q. Le

  2. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 75390-9069, USA

    Lu Q. Le

  3. UTSW Comprehensive Neurofibromatosis Clinic, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 75390-9069, USA

    Lu Q. Le

  4. Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 75390-9069, USA

    Lu Q. Le

  5. O’Donnell Brain Institute, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 75390-9069, USA

    Lu Q. Le

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Writing – original draft: BNS, AS, RMM, and LQL; Writing – review and editing: BNS, RMM, and LQL.

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Correspondence to Lu Q. Le.

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Somatilaka, B.N., Sadek, A., McKay, R.M. et al. Malignant peripheral nerve sheath tumor: models, biology, and translation. Oncogene 41, 2405–2421 (2022). https://doi.org/10.1038/s41388-022-02290-1

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