Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis

Our plain-English summary of Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis, by J.O. Blakeley, S.R. Plotkin (Neuro-oncology, 2016).

The study

• Authors: J.O. Blakeley, S.R. Plotkin
• Journal: Neuro-oncology
• Published: 2016;18(5):624-38
• Type of article: Review
• Cited by: 102 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN) are tumor-suppressor syndromes. Each syndrome is an orphan disease; however, the tumors that arise within them represent the most common tumors of the nervous system worldwide. Systematic investigation of the pathways impacted by the loss of function of neurofibromin (encoded byNF1) and merlin (encoded byNF2) have led to therapeutic advances for patients with NF1 and NF2. In the syndrome of SWN, the genetic landscape is more complex, with 2 known causative genes (SMARCB1andLZTR1) accounting for up to 50% of familial SWN patients. The understanding of the molecular underpinnings of these syndromes is developing rapidly and offers more therapeutic options for the patients. In addition, common sporadic cancers harbor somatic alterations inNF1(ie, glioblastoma, breast cancer, melanoma),NF2(ie, meningioma, mesothelioma) andSMARCB1(ie, atypical teratoid/rhabdoid tumors) such that advances in management of syndromic tumors may benefit patients both with and without germline mutations. In this review, we discuss the clinical and genetic features of NF1, NF2 and SWN, the therapeutic advances for the tumors that arise within these syndromes and the interaction between these rare tumor syndromes and the common tumors that share these mutations.

© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: [email protected].

In plain English

This article was a review, not a new study, and it did not study asbestos. The authors reviewed published research on three inherited tumor syndromes: neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis. They described the clinical features and genes of each condition and the research on treatments for the tumors that arise in them, which are mostly benign tumors of the nervous system. Mesothelioma appeared only once, in a list of common cancers that can carry changes in the NF2 gene. The authors counted 21 clinical trials for plexiform neurofibromas in NF1 and summarized trials run by other researchers. In one cited phase 2 imatinib trial, 6 of 36 participants (17%) had a response on imaging. In a cited early bevacizumab series in NF2, 6 of 10 people had at least a 20% reduction in tumor volume. The authors noted that no trials had yet focused on tumors in schwannomatosis. The authors concluded that these efforts had produced a number of small, early successes for tumors in NF1 and NF2, and that new and better drugs are still needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published research on NF1, NF2 and schwannomatosis
• Who was studied: No new study population. The review draws on published studies and clinical trials in patients with NF1, NF2 and schwannomatosis.
• Exposure: Not applicable. No asbestos, fiber or occupational exposure was studied. The subject is inherited genetic tumor syndromes and drug treatments for them. Mesothelioma is mentioned only as a cancer that can carry NF2 gene alterations.
• Main results:
  • The review reports 21 clinical trials for plexiform neurofibroma (pNF) in NF1, some of them ongoing.
  • Cited study, not this article: a phase 2 imatinib trial showed radiographic response in 6/36 (17%) of participants with pNF, aged 3 to 65 years.
  • Cited study, not this article: in a phase 1 selumetinib study, all 11 participants with pNF who could be evaluated for response had a decrease in tumor volume.
  • Cited study, not this article: in the initial bevacizumab experience in NF2-associated vestibular schwannoma, 6 of 10 participants had a reduction in tumor volume of at least 20%.
  • The authors reported that no clinical trials had focused specifically on schwannomas or meningiomas in schwannomatosis.
• The authors' conclusion: The authors concluded that collaborative efforts had produced a number of small, early successes for tumors in patients with NF1 and NF2, and that new and better drugs against NF-associated tumors are still needed.

Topics

Medical terms in this study, explained in our Lexicon: Merlin, Mesothelioma, Rhabdoid, Germline Mutation.

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