BRAF and MEK Targeted Therapies in Pediatric Central Nervous System Tumors.

BRAF is a component of the MAPK and PI3K/AKT/mTOR pathways that play a crucial role in cellular proliferation, differentiation, migration, and angiogenesis. Pediatric central nervous system tumors very often show mutations of the MAPK pathway, as demonstrated by next-generation sequencing (NGS), which now has an increasing role in cancer diagnostics. The MAPK mutated pathway in pediatric CNS tumors is the target of numerous drugs, approved or under investigation in ongoing clinical trials. In this review, we describe the main aspects of MAPK and PI3K/AKT/mTOR signaling pathways, with a focus on the alterations commonly involved in tumorigenesis. Furthermore, we reported the main available data about current BRAF and MEK targeted therapies used in pediatric low-grade gliomas (pLLGs), pediatric high-grade gliomas (pHGGs), and other CNS tumors that often present BRAF or MEK mutations. Further molecular stratification and clinical trial design are required for the treatment of pediatric CNS tumors with BRAF and MEK inhibitors.

GH Therapy in children and adolescents with Growth Hormone Deficiency during the first phase of COVID-19 lockdown: a survey in an Italian center.

BACKGROUND: Coronavirus Disease - 19 (COVID-19) had a profound impact on mental health of people and can influence the quality of life of children who need chronic therapies, affecting daily adherence to drug therapy and altering long-term outcomes. In Growth Hormone Deficiency (GHD) regular drug intake guarantees height improvement and, consequently, self-esteem of children. We conducted a survey to evaluate adherence to daily therapy and changes of height standard deviations in children with GHD during a pandemic-associated lockdown. METHODS: 30 children (17 boys and 13 girls) with aged between 7 and 18 years were examined during the observational period. Adherence to therapy (self-reported and also confirmed with a standardized questionnaire), height and growth velocity during treatment were analyzed. RESULTS: All of our patients reported a moderate to high level of adherence during the period of sanitary emergency (N=2 Morisky 7; N=28 Morisky 8). Adherence assessed by the Morisky Scale was in agreement in all cases with the self-reported one. Analysis of our data confirmed an improvement of the patients' height standard deviations, which could be related to the good adherence to growth hormone therapy during lockdown. CONCLUSIONS: We can hypothesize that limitations during the lockdown period have positively influenced adherence to therapy and, consequently, height standard deviations of children with GHD in substitution therapy. The evaluation of adherence carried out by our interview showed an increased regularity in hormonal administration due to various factors, such as the greatest amount of time spent indoors. The increased adherence is coherent with the results of our auxological evaluations, which showed an increase in percentiles and standard deviations of height, compared to chronological age.

Enlarged spinal nerve roots in RASopathies: Report of two cases.

RASopathies are a group of genetic conditions caused by germline variants in genes encoding signal transducers and modulators of the RAS-MAPK cascade. These disorders are multisystem diseases with considerable clinical overlap, even though distinct hallmarks are recognizable for each specific syndrome. Here we report on the presence of enlarged spinal nerve roots resembling neurofibromas, a typical neuroradiological finding of neurofibromatosis type 1, in two patients with a molecularly confirmed diagnosis of Noonan syndrome and cardio-facio-cutaneous syndrome, respectively. This evidence add enlarged spinal nerve roots as features shared among RASopathies. Future studies aiming to a better understanding of the molecular mechanisms leading to neurogenic tumor development in these patients are necessary to define their biological nature, evolution, prognosis and possible treatments.