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dc.contributor.authorPuglisi, M
dc.contributor.authorStewart, A
dc.contributor.authorThavasu, P
dc.contributor.authorFrow, M
dc.contributor.authorCarreira, S
dc.contributor.authorMinchom, A
dc.contributor.authorPunwani, R
dc.contributor.authorBhosle, J
dc.contributor.authorPopat, S
dc.contributor.authorRatoff, J
dc.contributor.authorde Bono, J
dc.contributor.authorYap, TA
dc.contributor.authorO''Brien, M
dc.contributor.authorBanerji, U
dc.date.accessioned2016-08-18T10:58:19Z
dc.date.issued2016-01
dc.identifier.citationOncology, 2016, 90 (5), pp. 280 - 288
dc.identifier.issn0030-2414
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/69
dc.identifier.eissn1423-0232
dc.identifier.doi10.1159/000444928
dc.description.abstractObjectives We hypothesised that it was possible to quantify phosphorylation of important nodes in the phosphatidylinositol 3-kinase (PI3K) pathway in cancer cells isolated from pleural effusions of patients with non-small cell lung cancer (NSCLC) and study their correlation to somatic mutations and clinical outcomes.Materials and methods Cells were immunomagnetically separated from samples of pleural effusion in patients with NSCLC. p-AKT, p-S6K and p-GSK3β levels were quantified by ELISA; targeted next-generation sequencing was used to characterise mutations in 26 genes.Results It was possible to quantify phosphoproteins in cells isolated from 38/43 pleural effusions. There was a significant correlation between p-AKT and p-S6K levels [r = 0.85 (95% confidence interval 0.73-0.92), p < 0.0001], but not p-AKT and p-GSK3β levels [r = 0.19 (95% confidence interval -0.16 to 0.5), p = 0.3]. A wide range of mutations was described and p-S6K was higher in samples that harboured at least one mutation compared to those that did not (p = 0.03). On multivariate analysis, p-S6K levels were significantly associated with poor survival (p < 0.01).Conclusion Our study has shown a correlation between p-AKT levels and p-S6K, but not GSK3β, suggesting differences in regulation of the distal PI3K pathway by AKT. Higher p-S6K levels were associated with adverse survival, making it a critically important target in NSCLC.
dc.formatPrint-Electronic
dc.format.extent280 - 288
dc.languageeng
dc.language.isoeng
dc.subjectHumans
dc.subjectCarcinoma, Non-Small-Cell Lung
dc.subjectLung Neoplasms
dc.subjectPleural Effusion, Malignant
dc.subjectRibosomal Protein S6 Kinases, 70-kDa
dc.subjectSignal Transduction
dc.subjectMutation
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectNeoplastic Cells, Circulating
dc.subjectPhosphatidylinositol 3-Kinase
dc.subjectGlycogen Synthase Kinase 3 beta
dc.titleCharacterisation of the Phosphatidylinositol 3-Kinase Pathway in Non-Small Cell Lung Cancer Cells Isolated from Pleural Effusions.
dc.typeJournal Article
dcterms.dateAccepted2016-02-23
rioxxterms.versionofrecord10.1159/000444928
rioxxterms.licenseref.startdate2016-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfOncology
pubs.issue5
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 Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicine Drug Development Unit (de Bono)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Pharmacology – Adaptive Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine Drug Development Unit (de Bono)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Thoracic Oncology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Thoracic Oncology/Thoracic Oncology (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Treatment of thoracic tumours
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Treatment of thoracic tumours/Treatment of thoracic tumours (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
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 Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicine Drug Development Unit (de Bono)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Pharmacology – Adaptive Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine Drug Development Unit (de Bono)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Thoracic Oncology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Thoracic Oncology/Thoracic Oncology (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Treatment of thoracic tumours
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Treatment of thoracic tumours/Treatment of thoracic tumours (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume90
pubs.embargo.termsNo embargo
icr.researchteamCancer Biomarkersen_US
icr.researchteamClinical Pharmacology – Adaptive Therapyen_US
icr.researchteamMedicine Drug Development Unit (de Bono)en_US
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
icr.researchteamThoracic Oncologyen_US
icr.researchteamTreatment of thoracic tumoursen_US
dc.contributor.icrauthorDe Bono, Johannen
dc.contributor.icrauthorBanerji, Udaien
dc.contributor.icrauthorCarreira, Suzanneen
dc.contributor.icrauthorPopat, Sanjayen
dc.contributor.icrauthorO'Brien, Maryen
dc.contributor.icrauthorYap, Timothyen
dc.contributor.icrauthorTurner, Lydiaen


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