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000307373 1001_ $$0P:(DE-He78)2bebef4e65bbcb341e31ca0999b69436$$aElHarouni, Dina$$b0$$eFirst author
000307373 245__ $$aIntegrative Multiomics and Drug Sensitivity Profiling Reveal Potential Biomarkers and Therapeutic Strategies in Pediatric Solid Tumors.
000307373 260__ $$aPhiladelphia, Pa.$$bAACR$$c2026
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000307373 500__ $$a#EA:B062#LA:B062# / 2026 Feb 2;86(3):773-784
000307373 520__ $$aCure rates for childhood malignancies using established therapy protocols have increased to an average of 80% but have reached a plateau. Moreover, survival rates are particularly low for some pediatric tumors-such as high-risk group 3 medulloblastomas, osteosarcomas, Ewing sarcomas, high-risk neuroblastomas, and high-grade gliomas-and dismal for patients with relapsed malignancies. A functional drug response profiling platform for pediatric solid and brain tumors has been established within the INFORM program to identify patient-specific vulnerabilities and biomarkers and to unravel molecular mechanisms associated with drug response profiles for clinical translation. In this study, we performed a multiomics analysis using drug sensitivity profiles, as well as genomic and transcriptomic data, of 81 pediatric solid tumor samples. The integrative analysis suggested two multiomics signatures associated with drug sensitivity. One signature distinguished neuroblastoma samples with sensitivity to navitoclax, a BCL2 family inhibitor. A second signature was specific to a subset of Wilms tumors harboring the SIX1 (Q177R) hotspot mutation that displayed high expression of MGAM, PTPN14, STAT4, and KDM2B and high sensitivity to MEK inhibitors. A patient-specific causal interaction network analysis suggested possible molecular interactions between MEK inhibitors and the SIX1 mutation in Wilms tumor samples. In conclusion, the integration of drug sensitivity profiling and multiomics data revealed potential biomarkers that may be associated with drug sensitivity in pediatric solid tumors. Patient-specific causal interaction network analysis further elucidated the interaction between inhibitors and signature biomarkers, providing insights that may inform clinical translation.The combination of multiomics analysis and drug sensitivity profiling identified two signatures related to drug sensitivity in pediatric solid tumors, contributing to the advancement of functional precision medicine and personalized treatment strategies. This article is part of a special series: Driving Cancer Discoveries with Computational Research, Data Science, and Machine Learning/AI .
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000307373 7001_ $$00000-0001-8536-8848$$aHernansaiz-Ballesteros, Rosa$$b1
000307373 7001_ $$0P:(DE-He78)2727b5cb63b52d0137d4f4e8f110ee7e$$aPeterziel, Heike$$b2$$udkfz
000307373 7001_ $$0P:(DE-He78)e5bb26ffbde307745ae396c2e829dac5$$aBalasubramanian, Gnanaprakash$$b3$$udkfz
000307373 7001_ $$0P:(DE-He78)1bae3784eb554a693b0e7ce03a20bdb8$$aPreviti, Christopher$$b4$$udkfz
000307373 7001_ $$0P:(DE-He78)2f592d9d8339bee07cca3956b7472b61$$aSchramm, Kathrin$$b5$$udkfz
000307373 7001_ $$0P:(DE-He78)261d2b84aded878003e6e35d18113831$$aBlattner-Johnson, Mirjam$$b6$$udkfz
000307373 7001_ $$0P:(DE-He78)36d0b1aeaf5a81ce289db680388c0adf$$aKabbe, Rolf$$b7$$udkfz
000307373 7001_ $$0P:(DE-He78)fae1bf941c5fd76cf5356ecfa1243cc4$$aJones, Barbara$$b8$$udkfz
000307373 7001_ $$0P:(DE-He78)55dfd5b374ab9bccdb49e06e91345571$$aOppermann, Sina$$b9
000307373 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b10$$udkfz
000307373 7001_ $$0P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9$$aPfister, Stefan$$b11$$udkfz
000307373 7001_ $$0P:(DE-He78)143af26de9d57bf624771616318aaf7c$$aWitt, Olaf$$b12$$udkfz
000307373 7001_ $$aSaez-Rodriguez, Julio$$b13
000307373 7001_ $$0P:(DE-He78)908367a659dea9e28dac34592b3c46e5$$aOehme, Ina$$b14$$udkfz
000307373 7001_ $$0P:(DE-He78)bff9e3e3d86865d2b0836bb8f3ce98f3$$aJäger, Natalie$$b15$$eLast author$$udkfz
000307373 7001_ $$aSchlesner, Matthias$$b16
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