A computational pipeline for comprehensive analysis of cancer, drugs, and target databases
Aditya Lahiri¹, PhD Sangeeta Shukla¹, PhD Eric Wafula¹, PhD Kelsey Keith¹, MS Yuanchao Zhang¹, PhD Dave Hill¹, MS Krutika S. Gaonkar¹ ̇² ̇³, MS Run Jin² ̇³, PhD Komal S. Rathi, ¹ ̇², MS Yuankun Zhu² ̇³, BS Bailey K. Farrow² ̇³,BS Daniel P. Miller² ̇³, MS Adam A. Kraya² ̇³, PhD Xiaoyan Huang² ̇³, MS Bo Zhang² ̇³, BS Zhuangzhuang Geng² ̇³, PhD Brian M. Ennis² ̇³, BS Ryan J. Corbett² ̇³, PhD Nicholas Van Kuren² ̇³, MS Matthew R. Lueder² ̇³ ̇⁴,MS Christopher Blackden² ̇³ MS Saksham Phul² ̇³ ,MS Miguel A. Brown² ̇³, MA Alex Sickler² ̇³, BS Asif T Chinwalla¹, MS,MBA Alvin Farrel¹ ̇⁵ ̇⁶, PhD Jo Lynne Rokita¹ ̇² ̇³, PhD Sharon J. Diskin⁵ ̇⁷, PhD Adam C. Resnick² ̇³, PhD John M. Maris ⁵ ̇⁶ ̇⁸, MD Sarah K. Tasian ⁵ ̇⁶ ̇⁸, MD Deanne Taylor¹ ̇⁹ PhD 1 Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA 2 Center for Data-Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA 3 Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA 4 Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA 5 Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA 6 Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA 7 Department of Pediatrics, University of Pennsylvania, Philadelphia, PA, 19104, USA 8 Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA 9 Department of Pediatrics, University of Pennsylvania Perelman Medical School, Philadelphia, PA, 19104, USA
Poster # 56
Pediatric cancers are rare and multifaceted diseases. Therapeutic advances of the last 50 years have increased the five-year survivorship for pediatric cancer patients in the US from 58% in 1975 to an estimated 85% in 2022. Furthermore, public sector efforts, such as the Gabriella Miller Kids First Research Act of 2014, have played a pivotal role in bringing resources dedicated to elucidating the underlying mechanism of pediatric cancers. Despite the efforts, pediatric cancers remain the leading cause of disease-related deaths in the US in children and adolescents. The RACE for Children Act of 2017 expanded the Food and Drug Administration (FDA) requirements for sponsors of therapeutic agents for adult cancer to assess their medications in pediatric populations. In response, the FDA Pediatric Molecular Target List (FDA-PMTL) was created, containing over 400 pediatric cancer gene targets of interest. This law required sponsors of therapeutic agents related to PMTL genes to test those agents in pediatric cancer. However, limited resources outline therapeutic agents tested in clinical trials for cancer for the PMTL genes. There is thus a need to integrate systematically and analyze the publicly available data to identify targets associated with therapeutic agents tested in pediatric cancers, especially agents used in registered clinical trials. To this end, we have developed a computational pipeline that integrates data and analyzes data from the following four public databases: Clinical Trials (clinicaltrials.gov), Open Targets (opentargets.org), Illuminating the Druggable Genome (IDG), and the FDA-PMTL and elucidates relationships between pediatric cancers, agents, and targets (here, genes). The curated merger of these databases allows the pipeline to (i) identify the existing agents and targets associated with pediatric cancer, (ii) find common targets for agents tested in registered clinical trials for pediatric and adult cancers, (iii) for each FDA-PMTL gene, summarize the associated pediatric cancers, adult cancers, and agents.