BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1909300004?filename=Park2019.xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1909300004?filename=Park2019.cpshttps://www.ebi.ac.uk/biomodels/model/download/MODEL1909300004?filename=Park2019.sedmlprimaryOK200Krishna Kumar TiwariNon-curatedL2V4https://www.ebi.ac.uk/biomodels/MODEL1909300004Oncology30719834falseBioModelsSBMLModelsPark2019 Cetuximab resistance in colorectal cancer2019MODEL1909300004Sang-Min ParkSang-Min Park, Chae Young Hwang, Sung-Hwan Cho, Daewon Lee, Jeong-Ryeol Gong, Soobeom Lee, Sohee Nam, Kwang-Hyun Cho30719834, Cetuximab (CTX), a monoclonal antibody against epidermal growth factor receptor, is being widely used for colorectal cancer (CRC) with wild-type (WT) KRAS. However, its responsiveness is still very limited and WT KRAS is not enough to indicate such responsiveness. Here, by analyzing the gene expression data of CRC patients treated with CTX monotherapy, we have identified DUSP4, ETV5, GNB5, NT5E, and PHLDA1 as potential targets to overcome CTX resistance. We found that knockdown of any of these five genes can increase CTX sensitivity in KRAS WT cells. Interestingly, we further found that GNB5 knockdown can increase CTX sensitivity even for KRAS mutant cells. We unraveled that GNB5 overexpression contributes to CTX resistance by modulating the Akt signaling pathway from experiments and mathematical simulation. Overall, these results indicate that GNB5 might be a promising target for combination therapy with CTX irrespective of KRAS mutation.. 7, 286. Laboratory for Systems Biology and Bio-inspired Engineering, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.ktiwari@ebi.ac.ukEMBL-EBICetuximab (CTX), a monoclonal antibody against epidermal growth factor receptor, is being widely used for colorectal cancer (CRC) with wild-type (WT) KRAS. However, its responsiveness is still very limited and WT KRAS is not enough to indicate such responsiveness. Here, by analyzing the gene expression data of CRC patients treated with CTX monotherapy, we have identified DUSP4, ETV5, GNB5, NT5E, and PHLDA1 as potential targets to overcome CTX resistance. We found that knockdown of any of these five genes can increase CTX sensitivity in KRAS WT cells. Interestingly, we further found that GNB5 knockdown can increase CTX sensitivity even for KRAS mutant cells. We unraveled that GNB5 overexpression contributes to CTX resistance by modulating the Akt signaling pathway from experiments and mathematical simulation. Overall, these results indicate that GNB5 might be a promising target for combination therapy with CTX irrespective of KRAS mutation.Systems analysis identifies potential target genes to overcome cetuximab resistance in colorectal cancer cells.Park Sang-Min SM, Hwang Chae Young CY, Cho Sung-Hwan SH, Lee Daewon D, Gong Jeong-Ryeol JR, Lee Soobeom S, Nam Sohee S, Cho Kwang-Hyun KHfalsePark2019 - Cetuximab resistance in colorectal cancer It's an experimental + mathematical paper explaining probable targets for Cetixumab resistance in colorectal cancer. 2019-09-302019-09-302019-09-30MODEL190930000430719834