Rhabdoid tumour are highly aggressive childhood cancers that are fatal in the majority of cases,

often within a year of diagnosis. These cancers carry mutations in SMARCB1, a gene involved in

regulating the function of other genes. Current treatment for rhabdoid tumours cures only around a

quarter of afflicted children and often results in life-changing side-effects in survivors. Little is

understood as to why treatment is effective in some children whilst not in others, or why the effect

of initially beneficial treatment quickly wears off. There is an urgent need to discover new

treatments with greater effectiveness as well as design molecular tests that can identify which

children will benefit from existing drugs. Our research is aimed at identifying which are the cellular

molecules that drive growth and spread of rhabdoid tumours, and to use this information to

nominate new treatment strategies and develop real-time diagnostic tests for personalising

treatment in patients.

This study will use tissue samples obtained from rhabdoid tumour patients as well as from a group

of closely related paediatric and adolescent cancers which similarly have SMARCB1 mutations. By

conducting comprehensive molecular profiling of these patient specimens, we will curate the

protein-specific molecular drivers in this tumour type, link this information to known drug

candidates and develop ways to predict for therapy response. In addition to the identification of

new drug targets, we expect our research will provide a means of estimating the sensitivity of an

individual patient’s cancer to available drugs ahead of starting treatment, enabling the development

of a personalised approach to treating rhabdoid tumours. Going forward, our work will provide the

basis for new anticancer drug trials in rhabdoid tumours (and other SMARCB1 mutant cancers)

that aim to establish effective and safe new treatments for these devastating diseases.