biostudies-literatureKim JNHLBI NIH HHSNCI NIH HHS2393-8https://www.ebi.ac.uk/biostudies/studies/S-EPMC4147888biostudies-literatureUnknown30(17)<h4>Motivation</h4>Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death in the United States. Targeted tyrosine kinase inhibitors (TKIs) directed against the epidermal growth factor receptor (EGFR) have been widely and successfully used in treating NSCLC patients with activating EGFR mutations. Unfortunately, the duration of response is short-lived, and all patients eventually relapse by acquiring resistance mechanisms.<h4>Result</h4>We performed an integrative systems biology approach to determine essential kinases that drive EGFR-TKI resistance in cancer cell lines. We used a series of bioinformatics methods to analyze and integrate the functional genetics screen and RNA-seq data to identify a set of kinases that are critical in survival and proliferation in these TKI-Bioinformatics (Oxford, England)Bioinformatics-driven discovery of rational combination for overcoming EGFR-mutant lung cancer resistance to EGFR therapy.PMC4147888P30 CA046934P50 CA058187P30CA046934R01 HL111674R21 HL106112R01CA127105R01 CA127105R01HL106112P50CA58187R01HL111674Tan ACKern JAMishra RFinigan JHKim JSingleton KRHeasley LEFarias-Hesson EMason RJVasu VTLeach SMYoo MKang JRamamoorthy PfalseBioinformatics-driven discovery of rational combination for overcoming EGFR-mutant lung cancer resistance to EGFR therapy.<h4>Motivation</h4>Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death in the United States. Targeted tyrosine kinase inhibitors (TKIs) directed against the epidermal growth factor receptor (EGFR) have been widely and successfully used in treating NSCLC patients with activating EGFR mutations. Unfortunately, the duration of response is short-lived, and all patients eventually relapse by acquiring resistance mechanisms.<h4>Result</h4>We performed an integrative systems biology approach to determine essential kinases that drive EGFR-TKI resistance in cancer cell lines. We used a series of bioinformatics methods to analyze and integrate the functional genetics screen and RNA-seq data to identify a set of kinases that are critical in survival and proliferation in these TKI-2014-01-01T00:00:00Z2014 Sep2026-04-30T08:29:01.597Z2019-03-27T01:34:49ZS-EPMC41478882481233910.1093/bioinformatics/btu323