• 56: Multiple RTK targeting as a therapeutic option in malignant pleural mesothelioma.

      Baird, A; Easty, D; Mohamed, B; Jarzabek, M; Shiels, L; Soltermann, A; Raeppel, S; McDonagh, L; Clarke, G; Crosbie-Staunton, K; et al. (2017-01)
    • Abstract CT117: Evaluation of the effect of crizotinib (CRZ) on the QT interval in patients with ALK-positive non-small cell lung cancer (NSCLC)

      Tan, W; Wilner, K; Lanzalone, S; Polli, A; Zierhut, M; Nickens, D; O'Byrne, K; Blackhall, Fiona H; Shaw, A; Salgia, R; et al. (2015-08-02)
    • Crizotinib versus chemotherapy in advanced ALK-positive lung cancer.

      Shaw, A; Kim, D; Nakagawa, K; Seto, T; Crinó, L; Ahn, M; De Pas, T; Besse, B; Solomon, B; Blackhall, Fiona H; et al. (2013-06-20)
      In single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK. Whether crizotinib is superior to standard chemotherapy with respect to efficacy is unknown.
    • Lungscape: resected non-small-cell lung cancer outcome by clinical and pathological parameters.

      Peters, S; Weder, W; Dafni, U; Kerr, K; Bubendorf, L; Meldgaard, P; O'Byrne, K; Wrona, A; Vansteenkiste, J; Felip, E; et al. (2014-11)
      The Lungscape project was designed to address the impact of clinical, pathological, and molecular characteristics on outcome in resected non-small- cell lung cancer (NSCLC).
    • Meta-analysis of individual patient data from randomized trials of chemotherapy plus cetuximab as first-line treatment for advanced non-small cell lung cancer.

      Pujol, J; Pirker, R; Lynch, T; Butts, C; Rosell, R; Shepherd, F; Vansteenkiste, J; O'Byrne, K; de Blas, B; Heighway, J; et al. (2014-02)
      Four randomized phase II/III trials investigated the addition of cetuximab to platinum-based, first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). A meta-analysis was performed to examine the benefit/risk ratio for the addition of cetuximab to chemotherapy.
    • Prevalence and Clinical Outcomes for Patients With ALK-Positive Resected Stage I to III Adenocarcinoma: Results From the European Thoracic Oncology Platform Lungscape Project.

      Blackhall, Fiona H; Peters, S; Bubendorf, L; Dafni, U; Kerr, K; Hager, H; Soltermann, A; O'Byrne, K; Dooms, C; Sejda, A; et al. (2014-07-28)
      The prevalence of anaplastic lymphoma kinase (ALK) gene fusion (ALK positivity) in early-stage non-small-cell lung cancer (NSCLC) varies by population examined and detection method used. The Lungscape ALK project was designed to address the prevalence and prognostic impact of ALK positivity in resected lung adenocarcinoma in a primarily European population.
    • Second ESMO consensus conference on lung cancer: pathology and molecular biomarkers for non-small-cell lung cancer.

      Kerr, K M; Bubendorf, L; Edelman, M J; Marchetti, A; Mok, T; Novello, S; O'Byrne, K; Stahel, R; Peters, S; Felip, E; et al. (2014-09)
      To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The Second ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on management of patients with non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, early stage disease, locally advanced disease and advanced (metastatic) disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on recommendations for pathology and molecular biomarkers in relation to the diagnosis of lung cancer, primarily non-small-cell carcinomas.
    • When RON MET TAM in mesothelioma: all druggable for one, and one drug for all?

      Baird, A; Easty, D; Jarzabek, M; Shiels, L; Soltermann, A; Klebe, S; Raeppel, S; MacDonagh, L; Wu, C; Griggs, K; et al. (2019)
      Malignant pleural mesothelioma (MPM) is an aggressive inflammatory cancer with a poor survival rate. Treatment options are limited at best and drug resistance is common. Thus, there is an urgent need to identify novel therapeutic targets in this disease in order to improve patient outcomes and survival times. MST1R (RON) is a trans-membrane receptor tyrosine kinase (RTK), which is part of the c-MET proto-oncogene family. The only ligand recognized to bind MST1R (RON) is Macrophage Stimulating 1 (MST1), also known as Macrophage Stimulating Protein (MSP) or Hepatocyte Growth Factor-Like Protein (HGFL). In this study, we demonstrate that the MST1-MST1R (RON) signaling axis is active in MPM. Targeting this pathway with a small molecule inhibitor, LCRF-0004, resulted in decreased proliferation with a concomitant increase in apoptosis. Cell cycle progression was also affected. Recombinant MST1 treatment was unable to overcome the effect of LCRF-0004 in terms of either proliferation or apoptosis. Subsequently, the effect of an additional small molecular inhibitor, BMS-777607 (which targets MST1R (RON), MET, Tyro3, and Axl) also resulted in a decreased proliferative capacity of MPM cells. In a cohort of MPM patient samples, high positivity for total MST1R by IHC was an independent predictor of favorable prognosis. Additionally, elevated expression levels of MST1 also correlated with better survival. This study also determined the efficacy of LCRF-0004 and BMS-777607 in xenograft MPM models. Both LCRF-0004 and BMS-777607 demonstrated significant anti-tumor efficacy in vitro, however BMS-777607 was far superior to LCRF-0004. The in vivo and in vitro data generated by this study indicates that a multi-TKI, targeting the MST1R/MET/TAM signaling pathways, may provide a more effective therapeutic strategy for the treatment of MPM as opposed to targeting MST1R alone.
    • When RON MET TAM: potential interventions for mesothelioma therapy.

      Baird, A; Easty, D; Mohamed, B; Jarzabek, M; Sheils, L; Soltermann, A; Raepell, S; McDonagh, L; Clarke, G; Crosbie-Staunton, K; et al. (2016)