Abstract A37: Synthetic lethality as a tool to reveal novel vulnerabilities in NF1-associated tumorigenesis

Neurofibromatosis Type 1 (NF1) is a common (1:2500 births) genetic disorder and cancer predisposition syndrome, caused by mutations in the tumor suppressor gene NF1. One of the known functions of the protein encoded by NF1 (neurofibromin) is that of a negative regulator of Ras pathway signaling, through its Ras-GAP activity. Among other symptoms, individuals with NF1 often develop benign tumors of the peripheral nervous system (called dermal or plexiform neurofibromas), originating from the Schwann cell linage or their precursors. While these benign tumors can cause significant pain and mobility problems, some (~10%) progress further to malignant peripheral nerve sheath tumors (MPNSTs) and are a leading cause of death among NF1 patients. Both plexiform neurofibromas and MPNSTs arise following loss of the remaining WT NF1 allele within the Schwann cell linage (or their precursors). It is believed the majority of NF1-associated MPNSTs originate from preexisting plexiform neurofibromas. Treatment options for the benign plexiform neurofibromas and MPNSTs are extremely limited, mostly relying on surgical resection and broad-spectrum chemotherapy. Finding new molecular targets for therapeutics effective against both benign tumors and MPNSTs are critical for improved patient outcomes and quality of life. The genetic basis of NF1 syndrome make it a top candidate for using synthetic lethal genetic and therapeutic approaches to uncover unique variabilities in NF1 deficient cells.We hav...
Source: Molecular Cancer Therapeutics - Category: Cancer & Oncology Authors: Tags: Finding Synthetic Lethal Interactions through Functional Genomics: Poster Presentations - Proffered Abstracts Source Type: research