MDB-34. LITHIUM AND RADIATION REDUCE TUMOUR GROWTH IN GROUP 3 MEDULLOBLASTOMA

Medulloblastoma (MB) is the most common high-grade paediatric brain tumour, accounting for ~20 % of all childhood CNS tumours. It is comprised of 4 distinct molecular subtypes, with Group 3 MB having the worst prognosis with an overall survival of around 50 %. Additionally, current treatments, especially radiotherapy (RT), come at a very high cost for the developing brain and result in permanent complications, including lower IQ, slower processing speed, as well as social problems and lifelong dependency. Lithium has been shown to protect neurogenesis and cognitive functions from the negative effects of RT on the juvenile brain in vivo and can therefore be hypothesised as a preventive treatment strategy to ameliorate these side effects. However, the effects and mechanisms of action of lithium on MB tumours remain largely unknown. In this study, we used GMYC GFP Group 3 MB cells (Mainwaring et al., 2023) to study the effects of lithium and RT in vitro, as well as creating a syngeneic model of Group 3 MB to study those effects in vivo. By using a whole brain immunostaining technique (iDISCO+) and light sheet microscopy, we created a 3D model of every tumour and quantified the tumour volume under different treatment conditions. Our results show that lithium – alone and in combination with radiation – significantly decreases Group 3 MB tumour growth both in vitro and in vivo. Additionally, we studied the transcriptomic changes induced by lithium, validating them through protein analysis that identified Klf4 as a potential effector of its underlying mechanism of action.