First Target Actionability Review on MDM2 in pediatric cancers published in the European Journal of Cancer

European Journal of Cancer 2020, 160:168-181 (doi:10.1016/j.ejca.2020.01.027)
For this extensive, systematic literature review the authors identified 162 relevant peer-reviewed publications, containing 343 separate data entries. After scoring by individual reviewers and adjudication the data entries scores for ‘effect size’ and ’experimental quality’ were visualized in a disease-specific heatmap for each preclinical Proof-of-Concept data module.
In summary, this systematic target actionability review supports clinical evaluation of MDM2-targeting compounds in NBL, RMS and HGG; however, combination of an MDM2 inhibitor plus chemotherapy would likely be most beneficial, in order to circumvent acquired resistance to MDM2 inhibition. Furthermore, our TAR demonstrates that while MDM2 can be amplified and/or expressed in OS patient samples, the prevalence of TP53 mutations cautions against moving forward with MDM2 inhibitors in this indication.