Work package leader:

Jan Molenaar (PMC), and Hubert Caron (Roche)

Objectives of the work package:

Target actionability in pediatric cancers

Description of the tasks:

In this work package we aim to perform a systematic validation of targeted compounds and corresponding actionable genes and pathways in the different pediatric solid tumor entities prior to the in vitro and in vivo testing phase using relevant literature and the existing (epi)genomic and transcriptomic datasets of all entities in question. We will also map these with the portfolios of the participating pharma partners to enable a first prioritization of compounds for in vivo testing. With this approach, we should be able to select tumor types that will most likely respond to the targeted interventions; this will result in more efficient use of the PDX systems. The pipeline will encompass a systematic literature review followed by in silico analysis of the actionable events.


Objective 1: Definition of minimally-required preclinical proof-of-concept (POC) packages for ‘Target Actionability’.
Objective 2: Systematic literature reviews of pediatric ‘target actionability' for >6 drug targets/pathways matching the pipelines of the pharma partners.
Objective 3: Target aberration/activation patterns in clinical pediatric tumor series.