Essential signaling in NF2 loss-related tumours: the therapeutic potential of CRL4^DCAF1 and mTOR combined inhibition

Neurofibromatosis 2 (NF2) was first identified as the tumor suppressor gene mutated in NF2 hereditary cancer syndrome (1). In this syndrome, patients develop multiple tumors of the nervous system including schwannomas, meningiomas and ependymomas that often require treatment with surgery or radiotherapy. While inherited mutations in NF2 leading to NF2 syndrome are relatively uncommon (with an incidence of approximately 1 in 25,000), somatic NF2 mutations are also observed in sporadic tumors (2). Specifically, NF2 gene inactivation has been reported in a significant proportion of sporadic meningiomas, vestibular schwannomas and malignant mesotheliomas (3-6).