With the aim of introducing molecular profiling of paediatric patient tumours, we undertook a review of the literature to determine which molecular aberrations to include. We started with the list of genes included in the study by Von Hoff et al (J Clin Oncol 28:4877-4883, 2010), which formed the basis for this project. We included additional genes that are now routinely assayed by the tumour profiling service Caris. Further genes, which have been found to be important in the pathophysiology of childrens’ cancer were added, to bring our list to a total of 112 genes.
The list of genes has been ranked according to whether one or more drugs are available, for which there is:-
1. Clinical evidence of safety and efficacy in children and a clinically demonstrated target-associated response.
2. Clinical evidence of safety, efficacy in children and pre-clinical demonstration of a target-associated response.
3. Clinical evidence of safety, efficacy in adults and a clinically demonstrated target-associated response.
4. Clinical evidence of safety, efficacy in adults and pre-clinical demonstration of a target-associated response.
5. In vivo evidence of efficacy and a demonstrated target-associated response.
6. In vitro evidence of efficacy and a demonstrated target-associated response.
This process has identified eighty three genes that fit criteria 1 to 4. There are currently FDA approved therapies available for almost 80% of these targets, and drugs targeting many of the remaining genes are currently in stage 3 clinical trials. Ninety per cent of the final list of genes has been reported in the literature to have a role in childhood cancer.
Current objectives
We are now designing assays to measure expression of these genes in cancer and normal cell lines, and in fresh and stored tumour bank samples representative of the major childhood cancer subtypes. We will also be analysing gene mutations using targeted next generation sequencing.