2020
Discernment between candidate mechanisms for KRAS G13D colorectal cancer sensitivity to EGFR inhibitors
McFall T, Schomburg N, Rossman K, Stites E. Discernment between candidate mechanisms for KRAS G13D colorectal cancer sensitivity to EGFR inhibitors. Cell Communication And Signaling 2020, 18: 179. PMID: 33153459, PMCID: PMC7643456, DOI: 10.1186/s12964-020-00645-3.Peer-Reviewed Original ResearchConceptsKRAS mutationsKRAS G13DEGFR inhibitorsColorectal cancerSensitivity to EGFR inhibitorsRas-GTP levelsSensitivity to cetuximabClinical trial evidenceWild-type RasGTPase activityKRAS G13D mutationBind NF1Tumor suppressor NF1EGFR inhibitionG13D mutationKRASCetuximabBiophysical studiesTrial evidenceG13DWild-typeNF1MutationsCellular modelEGFR
2019
A systems mechanism for KRAS mutant allele–specific responses to targeted therapy
McFall T, Diedrich J, Mengistu M, Littlechild S, Paskvan K, Sisk-Hackworth L, Moresco J, Shaw A, Stites E. A systems mechanism for KRAS mutant allele–specific responses to targeted therapy. Science Signaling 2019, 12 PMID: 31551296, PMCID: PMC6864030, DOI: 10.1126/scisignal.aaw8288.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorWild-type Ras activationColorectal cancerSensitivity to EGFR inhibitionEpidermal growth factor receptor inhibitionKRAS mutantEGFR-independent mannerAllele-specific responsesRas activationGrowth factor receptorTumor suppressor neurofibrominPatient tumorsAntibody cetuximabTargeted therapyMechanisms of EGFR signalingCRC patientsEGFR inhibitionCancer treatment decisionsRAS mutationsFactor receptorKRASTherapeutic strategiesTreatment decisionsEGFR signalingPatientsModeling cell line-specific recruitment of signaling proteins to the insulin-like growth factor 1 receptor
Erickson KE, Rukhlenko OS, Shahinuzzaman M, Slavkova KP, Lin YT, Suderman R, Stites EC, Anghel M, Posner RG, Barua D, Kholodenko BN, Hlavacek WS. Modeling cell line-specific recruitment of signaling proteins to the insulin-like growth factor 1 receptor. PLOS Computational Biology 2019, 15: e1006706. PMID: 30653502, PMCID: PMC6353226, DOI: 10.1371/journal.pcbi.1006706.Peer-Reviewed Original ResearchConceptsReceptor tyrosine kinasesSrc homology 2Autophosphorylation sitesInsulin-like growth factor 1 receptorGrowth factor 1 receptorFactor 1 receptorPTB domain-containing proteinsCopy numberDomain-containing proteinsPhosphotyrosine-binding (PTB) domainProtein copy numbersMultiple autophosphorylation sitesProtein abundance profilesMultiple signaling proteinsShort linear motifsOutcome of competitionCell line-specific modelsHomology 2Cytoplasmic domainSignaling proteinsLinear motifsTyrosine kinaseEffects of competitionRule-based modeling approachRelative abundance