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dc.contributor.authorVyse, S
dc.contributor.authorHowitt, A
dc.contributor.authorHuang, PH
dc.date.accessioned2017-05-23T16:29:14Z
dc.date.issued2017-06
dc.identifier.citationJournal of molecular biology, 2017, 429 (12), pp. 1767 - 1786
dc.identifier.issn0022-2836
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/657
dc.identifier.eissn1089-8638
dc.identifier.doi10.1016/j.jmb.2017.04.018
dc.description.abstractDespite the recent approval of third-generation therapies, overcoming resistance to epidermal growth factor receptor (EGFR) inhibitors remains a major challenge in non-small cell lung cancer. Conceptually, synthetic lethality holds the promise of identifying non-intuitive targets for tackling both acquired and intrinsic resistance in this setting. However, translating these laboratory findings into effective clinical strategies continues to be elusive. Here, we provide an overview of the synthetic lethal approaches that have been employed to study EGFR inhibitor resistance and review the oncogene and non-oncogene signalling mechanisms that have thus far been unveiled by synthetic lethality screens. We highlight the potential challenges associated with progressing these discoveries into the clinic including context dependency, signalling plasticity, and tumour heterogeneity, and we offer a perspective on emerging network biology and computational solutions to exploit these phenomena for cancer therapy and biomarker discovery. We conclude by presenting a number of tangible steps to bolster our understanding of fundamental synthetic lethality mechanisms and advance these findings beyond the confines of the laboratory.
dc.formatPrint-Electronic
dc.format.extent1767 - 1786
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectCarcinoma, Non-Small-Cell Lung
dc.subjectEpidermal Growth Factor
dc.subjectAntineoplastic Agents
dc.subjectDrug Resistance
dc.subjectGene Regulatory Networks
dc.subjectDrug Discovery
dc.subjectErbB Receptors
dc.subjectBiomarkers, Tumor
dc.subjectSynthetic Lethal Mutations
dc.titleExploiting Synthetic Lethality and Network Biology to Overcome EGFR Inhibitor Resistance in Lung Cancer.
dc.typeJournal Article
dcterms.dateAccepted2017-04-27
rioxxterms.versionofrecord10.1016/j.jmb.2017.04.018
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-06
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJournal of molecular biology
pubs.issue12
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Protein Networks
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular and Systems Oncology
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Protein Networks
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular and Systems Oncology
pubs.publication-statusPublished
pubs.volume429
pubs.embargo.termsNo embargo
icr.researchteamProtein Networksen_US
icr.researchteamMolecular and Systems Oncologyen_US
dc.contributor.icrauthorVyse, Simonen
dc.contributor.icrauthorHuang, Paulen


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