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Highlights d CBL0137 inhibits DIPG tumor growth and restores H3K27me3 through FACT inhibition d Co-administration of CBL0137 and panobinostat enhances survival in DIPG xenografts d CBL0137 and panobinostat synergistically inhibit the Rb/ E2F1 pathway and restore H3K27me3

Biomarkers which better match anticancer drugs with cancer driver genes hold the promise of improved clinical responses and cure rates. We developed a precision medicine platform of rapid highthroughput drug screening (HTS) and patient-derived xenografting (PDX) of primary tumor tissue, and evaluated its potential for treatment identification among 56 consecutively enrolled high-risk pediatric cancer patients, compared with conventional molecular genomics and transcriptomics. Drug hits were seen in the majority of HTS and PDX screens, which identified therapeutic options for 10 patients for whom no targetable molecular lesions could be found. Screens also provided orthogonal proof of drug efficacy suggested by molecular analyses and negative results for some molecular findings. We identified treatment options across the whole testing platform for 70% of patients. Only molecular therapeutic recommendations were provided to treating oncologists and led to a change in therapy in 53% of patients, of whom 29% had clinical benefit. These data indicate that in vitro and in vivo drug screening of tumor cells could increase therapeutic options and improve clinical outcomes for high-risk pediatric cancer patients.

Glanzmann's thrombasthenia (GT) is a rare, congenital, and moderate to severe platelet disorder. The bleeding time is increased, due to lack of platelet aggregation, since the patients with GT have deficient or dysfunctional integrin membrane glycoproteins IIb and IIIa essential for platelet aggregation. Children with GT are mostly diagnosed very early in life due to the spontaneous and unexplained mucocutaneous bleeding. It is quite a challenging task when any surgery is indicated for children with GT. This case report is about the medical and surgical management of an 11-year-old girl diagnosed with Glannzmann's thrombasthenia who had to undergo a maxillary cyst enucleation.