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Last Updated: 10/10/18

Hyperactive RAS SPOREs

Tumorigenesis has been viewed as a process in which normal developmental programs are dysregulated, leading to aberrant cellular proliferation and differentiation. These processes lead to a failure to respect normal tissue boundaries and abnormal response to multiple inhibitory microenvironmental cues. The RASopathies are developmental syndromes caused by mutations in various genes capable of altering the function of RAS family proteins and Mitogen-activated protein kinases (MAPKs) that control intracellular signal transduction. Neurofibromatosis type 1 (NF1) is the most frequent RASopathy syndrome that occurs in 1:3500 live births. This syndrome is caused by mutations of the NF1 tumor suppressor gene that functions as a GTPse activating protein for p21RAS. Individuals with NF1 have a high predisposition to plexiform neurofibromas, a premalignant tumor that causes major morbidity and mortality in approximately 100,000 individuals in the US and Europe alone.

The Developmental and Hyperactive RAS Tumor SPORE (DHAR Tumor SPORE) focuses on devising better treatment for cancers and pre-malignant conditions associated with NF1 mutations including plexiform neurofibroma (pNF), malignant peripheral nerve sheath tumors (MPNST), juvenile myelomonocytic leukemia (JMML), and subsequent malignant neoplasms (SMN) in NF1 patients receiving radiation and chemotherapy for primary tumors.