Determining effective radiation / drug combinations for paediatric cancers

TC was most effective in 11q23 translocated cells with low basal PU.1 expression, significantly increased PU.1 expression with treatment, and decreased non-canonical NFκB expression. MuSIC also identified two antifungals, clotrimazole and econazole nitrate, which induced differential cell death between cells cultured in delipidated (DL) media to mimic the leukaemic-CNS environment, and normal pAML cell lines. Finally, the screen identified two triple combinations including both estropipate and posaconazole with either methenamine hippurate or pravastatin, which were effective up to 72 h with 2 Gy irradiation, in a SHH-subtype medulloblastoma cell line.<br><br> This study identified agents with attractive safety profiles as single agents, and results to date demonstrate their effectiveness in vitro in pAML, CNS-pAML and medulloblastoma.

Further validation is required in more clinically relevant models to elucidate their potential to be utilised clinically; to mitigate the acute and late side-effects caused by current standard of care treatments. <br><br><i>Thesis is embargoed until 31 July 2027.</i>