biostudies-literatureLau LMSAustralian Cancer Research FoundationCure Brain Cancer FoundationCancer Therapeutics Cooperative Research CentreKids Cancer AllianceRobert Connor Dawes FoundationKids' Cancer ProjectNational Health and Medical Research CouncilAustralian Lions Childhood Cancer Research FoundationUniversity of New South Walese14608https://www.ebi.ac.uk/biostudies/studies/S-EPMC8988207biostudies-literatureUnknown14(4)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 high-throughput 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 identifEMBO molecular medicineIn vitro and in vivo drug screens of tumor cells identify novel therapies for high-risk child cancer.PMC8988207APP1157871APP1059804Norris MDTsoli MZiegler DSUng CXie JStrong PAEden GMayoh CChow SOTyrrell VTrebilcock PFox SBGrebert Wade DFailes TWGifford ALau LMSCadiz RWarby MAlfred SBatey DDalla-Pozza LLock RBManouvrier EArndt GMPinese MFletcher JIThomas DMTucker KMFellowes AMorgan LTGopalakrishnan ALim JYSaletta FEkert PGHaber MWong MJoshi SBarahona PKamili AByrne JAMacKenzie KLKhan ACowley MJSpan MMcCowage GBWadham CMould EVAMarshall GMKhuong-Quang DATrahair TNKumar AfalseIn vitro and in vivo drug screens of tumor cells identify novel therapies for high-risk child cancer.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 high-throughput 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 identif2022-01-01T00:00:00Z2022 Apr2025-05-18T12:03:21.736Z2025-05-18T12:03:21.736ZS-EPMC89882073492779810.15252/emmm.202114608