Beth Stronach, PhD
Scientist Administrator, Office of Research, Health Sciences, University of Pittsburgh
 

From RAS to RASopathies: Drug Repositioning for Rare Diseases

Aberrant pathogenic signaling via the cellular RAS/MAPK pathway is responsible for a large group of congenital syndromes collectively termed 'the RASopathies'. These include: Noonan/Noonan-related (NS/ NSML/ NSLAH/ Cbl), cardio-facio-cutaneous (CFCS), Costello (CS), and Legius (LS) syndromes, as well as Neurofibromatosis 1 (NF1); additional conditions (e.g., SYNGAP1 syndrome, CM-AVM, CCLA) and cases of mosaicism, which carry hyperactive RAS/MAPK alleles, contribute to wide variability in clinical presentation and treatment needs. The entire spectrum of clinical features can pose substantial long-term medical, financial, and social burdens on families, from the prenatal period across the lifespan. With novel therapeutic assets in the oncology space to target RAS proteins directly or their regulators, the RASopathies may benefit from drug repurposing for effective treatments.