title: Inferences of drug responses in cancer cells from cancer genomic features and compound chemical and therapeutic properties.
abstract: Accurately predicting the response of a cancer patient to a therapeutic agent is a core goal of precision medicine. Existing approaches were mainly relied primarily on genomic alterations in cancer cells that have been treated with different drugs. Here we focus on predicting drug response based on integration of the heterogeneously pharmacogenomics data from both cell and drug sides. Through a systematical approach, named as PDRCC (Predict Drug Response in Cancer Cells), the cancer genomic alterations and compound chemical and therapeutic properties were incorporated to determine the chemotherapeutic response in cancer patients. Using the Cancer Cell Line Encyclopedia (CCLE) study as the benchmark dataset, all pharmacogenomics data exhibited their roles in inferring the relationships between cancer cells and drugs. When integrating both genomic resources and compound information, the prediction coverage was significantly increased. The validity of PDRCC was also supported by its effective in uncovering the unknown cell-drug associations with database and literature evidences. It set the stage for clinical testing of novel therapeutic strategies, such as the sensitive association between cancer cell 'A549_LUNG' and compound 'Topotecan'. In conclusion, PDRCC offers the possibility for faster, safer, and cheaper the development of novel anti-cancer therapeutics in the early-stage clinical trails.
authors.affiliation: Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, 810001 China.
authors.forename: Yongcui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD 20850, USA.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Fang
authors.affiliation: Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, 810001 China.
authors.forename: Shilong
authors.initials: S
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D023281:Genomics; D006801:Humans; D020128:Inhibitory Concentration 50; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009928:Organ Specificity; D012372:ROC Curve
chemical_list: D000970:Antineoplastic Agents