dc.contributor.author | Puglisi, M | |
dc.contributor.author | Stewart, A | |
dc.contributor.author | Thavasu, P | |
dc.contributor.author | Frow, M | |
dc.contributor.author | Carreira, S | |
dc.contributor.author | Minchom, A | |
dc.contributor.author | Punwani, R | |
dc.contributor.author | Bhosle, J | |
dc.contributor.author | Popat, S | |
dc.contributor.author | Ratoff, J | |
dc.contributor.author | de Bono, J | |
dc.contributor.author | Yap, TA | |
dc.contributor.author | O''Brien, M | |
dc.contributor.author | Banerji, U | |
dc.date.accessioned | 2016-08-18T10:58:19Z | |
dc.date.issued | 2016-01-01 | |
dc.identifier.citation | Oncology, 2016, 90 (5), pp. 280 - 288 | |
dc.identifier.issn | 0030-2414 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/69 | |
dc.identifier.eissn | 1423-0232 | |
dc.identifier.doi | 10.1159/000444928 | |
dc.description.abstract | OBJECTIVES: 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.format | Print-Electronic | |
dc.format.extent | 280 - 288 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | KARGER | |
dc.subject | Humans | |
dc.subject | Carcinoma, Non-Small-Cell Lung | |
dc.subject | Lung Neoplasms | |
dc.subject | Pleural Effusion, Malignant | |
dc.subject | Ribosomal Protein S6 Kinases, 70-kDa | |
dc.subject | Signal Transduction | |
dc.subject | Mutation | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Aged, 80 and over | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Neoplastic Cells, Circulating | |
dc.subject | Phosphatidylinositol 3-Kinase | |
dc.subject | Glycogen Synthase Kinase 3 beta | |
dc.title | Characterisation of the Phosphatidylinositol 3-Kinase Pathway in Non-Small Cell Lung Cancer Cells Isolated from Pleural Effusions. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-02-23 | |
rioxxterms.versionofrecord | 10.1159/000444928 | |
rioxxterms.licenseref.startdate | 2016-01 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Oncology | |
pubs.issue | 5 | |
pubs.notes | No 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-status | Published | |
pubs.volume | 90 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Cancer Biomarkers | |
icr.researchteam | Clinical Pharmacology – Adaptive Therapy | |
icr.researchteam | Medicine Drug Development Unit (de Bono) | |
icr.researchteam | Prostate Cancer Targeted Therapy Group | |
icr.researchteam | Thoracic Oncology | |
icr.researchteam | Treatment of thoracic tumours | |
dc.contributor.icrauthor | Carreira, Suzanne | |
dc.contributor.icrauthor | Minchom, Anna | |
dc.contributor.icrauthor | De Bono, Johann | |
dc.contributor.icrauthor | Banerji, Udai | |