New markers to select children with cancer for trials with PARP inhibitors

The outcome for children with cancer is poor when the disease returns and we need better treatments for children with cancer.

Testing the gene makeup of paediatric tumours is now standard in Europe for children where the disease returns. The ESMART trial is a new clinical trial for children with cancer which contains many different treatment arms with novel drugs, and the idea is to match the gene changes in the tumour to the right novel drug treatment.

Two arms of this trial investigate a drug called PARP inhibitor (PARPi). In adult cancer patients, changes in genes called BRCA1and 2 are linked with response to treatment. In the lab, paediatric tumours respond to PARPi, although they do not have changes in the BRCA genes.This project aims to identify better markers to select paediatric patients for PARPi treatment.

Clinical and genetic data in some patients in the trial showed that 3 out of 5 children who benefited from PARPi had changes in a gene called ATM, but we also know that another gene (SLFN11) and the message which genes make (mRNA) may be important in the response to treatment. We plan to assess the presence of ATM and SLFN11 expression in tumour tissue through a technique called staining, and to analyse the mRNA from the tumour tissue. We will investigate tumour tissue from ~110 patients and we will investigate blood of neuroblastoma patients at time points throughout treatment to see if we can detect gene damage (a sign for cell death) in tumour cells found in blood which could be an early marker for response.

Through this analysis we will find better markers to select children for PARPi treatment.