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Tumorigenesis in neurofibromatosis type 1: role of the microenvironment

Oncogene volume 40, pages 5781–5787 (2021)Cite this article

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Abstract

Neurofibromatosis Type 1 (NF1) is one of the most common inherited neurological disorders and predisposes patients to develop benign and malignant tumors. Neurofibromas are NF1-associated benign tumors but can cause substantial discomfort and disfigurement. Numerous studies have shown that neurofibromas arise from the Schwann cell lineage but both preclinical mouse models and clinical trials have demonstrated that the neurofibroma tumor microenvironment contributes significantly to tumorigenesis. This offers the opportunity for targeting new therapeutic vulnerabilities to treat neurofibromas. However, a translational gap exists between deciphering the contribution of the neurofibroma tumor microenvironment and clinically applying this knowledge to treat neurofibromas. Here, we discuss the key cellular and molecular components in the neurofibroma tumor microenvironment that can potentially be targeted therapeutically to advance neurofibroma treatment.

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Fig. 1: Clinical manifestations of neurofibroma.
Fig. 2: Components of neurofibroma tumor microenvironment.
Fig. 3: Signaling pathways regulating the functions of NFAFs.
Fig. 4: Proposed interactions between Schwann cells and fibroblasts in neurofibroma.

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Acknowledgements

LQL is the Thomas L. Shield, M.D. Endowed Professor in Dermatology. He held a Career Award for Medical Scientists from the Burroughs Wellcome Fund, and is supported by funding from the National Cancer Institute of the NIH (R01 CA166593) and the Developmental and Hyperactive RAS Tumor SPORE (U54 CA196519); the US Department of Defense (W81XWH-21-1-0651); the Neurofibromatosis Therapeutic Acceleration Program; the NF1 Research Consortium Fund; and the Giorgio Foundation.

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Authors and Affiliations

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

    Chunhui Jiang, Renee M. McKay & Lu Q. Le

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

    Lu Q. Le

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

    Lu Q. Le

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

    Lu Q. Le

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Writing – Original Draft: CJ, RMM, and LQL; Writing – Review and Editing: CJ, RMM, and LQL.

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Correspondence to Lu Q. Le.

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Jiang, C., McKay, R.M. & Le, L.Q. Tumorigenesis in neurofibromatosis type 1: role of the microenvironment. Oncogene 40, 5781–5787 (2021). https://doi.org/10.1038/s41388-021-01979-z

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