Investigation of small non coding RNAs in pediatric gliomas
pLGGs are the most common subtype of tumours that arise in the developing brains of children. Non-resectable pLGGs are highly frequent and associated with extensive morbidities, a large proportion of survivors show indeed long-term neurocognitive and psychosocial deficits. They include, but are not limited to, growth hormone deficiency, epilepsy, vision loss, impaired motor skills, memory dysfunction and reduced IQ, devastating outcomes that make critical the improvement of long-term outcome for survivors (Sexton-Oates et al., 2015). In recent years, next generation sequencing technologies have helped in understanding genetic lesions typically expressed in these tumours, holding promise as potential targets for novel therapies. However, since the clinical course of pLGGs is more similar to that of a chronic disease and the most commonly used chemotherapeutic agents often cause extensive morbidity, there is an urgent need in the development of new treatment strategies with the aim of reducing morbidity rather than increase survival. The discovery of epigenetic variations could play a pivotal role in the treatment of pLGGs. In this context, microRNAs have been highlighted as key players in tumour development, progression and/or recurrence. However, due to the high histological heterogeneity of pLGGs and to the complexity in obtaining fresh frozen tumour samples free from healthy tissue, data already available on microRNAs in pLGGs are scanty and far from conclusive. This project aims to trigger a fundamental transformation in the management of the huge proportion of pLGGs not amenable of complete surgical resection that still are a major clinical challenge. With this study, I propose to unravel microRNAs involved in the initiation and progression of pLGGs in order to identify novel potential candidates for molecular therapeutic targeting, opening new perspectives in pLGGs treatment. MicroRNAs could be applied not only in clinical trials as single treatment agents to obtain more effective and less toxic therapies, but also in combination with conventional chemo-radiotherapy to sensitize cancer cells. Furthermore, until now the absence of patients-derived cellular models of pLGGs has represented the main hurdle for an accurate study of their biology. Thanks to the primary patients¿ derived cells we established in the laboratory, I will have the chance to use short-term primary pLGG cells as cellular models to analyse the biological effects underlying the modulation of the microRNAs of interest in order to define their relevance in the tumorigenic signal activation and/or maintenance.
Sexton-Oates A. et al., Annals of Oncology 2015