NF2 Expanded Problem Tracks and Vision for Ongoing Investigation
The main issue with NF2 is that patients develop tumors in the central nervous system (schwannoma, meningioma, ependymoma), slowly knocking out senses and body functions (hearing for most, facial paralysis and sight/muscles/sensory functions for some). The “hallmark” of NF2 is vestibular schwannoma, a benign tumor emanating from the sheath of the VIIIth cranial nerve (vestibulocochlear nerve). NF2 patients carry one mutated NF2 allele in their germline and the second NF2 allele is inactivated somatically in the tumors following the classic Knudson’s “Two-hit hypothesis” for tumor suppressor genes. Somatic mutations of the NF2 gene are also found in sporadic schwannoma, meningioma, ependymomas as well as in other tumors types that are not typically associated with familial NF2, such as malignant mesothelioma.
All the ‘tracks’ below are ways to find out why these tumors are there, what makes them grow and most importantly how to stop them.
Is NF2 solely driven by a mutation in the “NF2 gene”, or is there more?
Is inactivation of NF2 gene the only reason for people to develop schwannomas, or might there be other gene alterations that influence tumor behaviour? What other affected genes could play a role in the formation and growth of these tumors?
Is the EGFR mutation in this tumor genome relevant for tumor formation and growth?
We’ve identified a somatic mutation in the EGFR gene that may play a role in the tumor development. Can you validate or invalidate that hypothesis? How?
What other hypotheses can we generate for why NF2-related tumors start forming and growing?
Are there any drugs that have not been looked at yet that may help mitigate tumor growth (like CBD)? What could be the reason for the tumor to start growing? What could be the reasons for the tumors to grow at different rates?
Which drugs have been studied already and what can we learn from that?
Which drugs have been studied so far for NF2-related tumors, and how do they rank up? Are there any drugs out there that show potential and are worth investigating more? Is there a potential gene association with this drug we may look into? What genes are targeted by any one of those drugs, and how do they affect the genetic pathways of the NF2 gene?
What other data may be interesting to learn from?
What kind of data would we need for people with NF2 in order to find out what drives tumor growth and to devise personalized treatments? Tumors, Blood, Whole genome, Proteomics, Metabolomics, -Omics, microbiome, environmental effects, lifestyle, diet.