Clinical Research Directory

Solid Tumors in RASopathies

RASopathies are a group of syndromes, caused by variants of genes involved in the regulation of the Ras/MAP/ERK pathway. This intracellular transduction pathway profoundly affects embryogenic development, organogenesis, synaptic plasticity and neuronal growth. RASopathies are characterized by multi-organ involvement, growth delay, premature aging and haemato-oncological manifestations. Based on evidences provided by literature, cancer screening protocols are applied in some individuals affected by RASopathies, even though detailed information about prevalence and molecular pathogenesis of such tumors is still not clearly elucidate.

Effect of RAS/MAPK Pathway Hyperactivation on Growth' and Bone' Profile of the RASopathies

Costello syndrome (CS) and cardio-facio cutaneous syndrome (CFCS) belongs to RASopathies, a group of multisystemic disorders caused by unregulated signalling through the RAS/MAPK pathway, an intracellular signalling pathway regulating multiple processes such as cellular proliferation, differentiation, survival, apoptosis and also contributing to oncogenesis. They share a recognizable facial appearance, aged appearance, growth delay, muscle-skeletal anomalies, heart defects, neuropsychological features, skin and ocular abnormalities, and cancer predisposition. Even though life expectancy of individuals with CS and CFCS has increased in the last years due to the improvement of patients' care and a more effective prevention of comorbidities, some of the most challenging aspects impacting on everyday living such as growth failure, accelerate senescence and skeletal-muscle defects, still need to be fully understood. This statement underlies the need to improve clinical research protocols with more innovative techniques (multi-omics profiling) in order to better understand the effect of RAS/MAPK pathway hyperactivations on different systems and to define possible personalized treatments.