1. A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer.

    Cell 162(1):146 (2015) PMID 26140595

    KRAS is one of the most frequently mutated oncogenes in human cancer. Despite substantial efforts, no clinically applicable strategy has yet been developed to effectively treat KRAS-mutant tumors. Here, we perform a cell-line-based screen and identify strong synergistic interactions between cell...
  2. Implementation of Amplicon Parallel Sequencing Leads to Improvement of Diagnosis and Therapy of Lung Cancer Patients.

    Journal of Thoracic Oncology 10(7):1049 (2015) PMID 26102443

    The Network Genomic Medicine Lung Cancer was set up to rapidly translate scientific advances into early clinical trials of targeted therapies in lung cancer performing molecular analyses of more than 3500 patients annually. Because sequential analysis of the relevant driver mutations on fixated ...
  3. Spatial Tumor Heterogeneity in Lung Cancer with Acquired Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Resistance: Targeting High-Level MET-Amplification and EGFR T790M Mutation Occurring at Different Sites in the Same Patient.

    Journal of Thoracic Oncology 10(6):e40 (2015) PMID 26001148

  4. ROS1 rearrangements in lung adenocarcinoma: prognostic impact, therapeutic options and genetic variability.

    Oncotarget 6(12):10577 (2015) PMID 25868855 PMCID PMC4496376

    While recent data show that crizotinib is highly effective in patients with ROS1 rearrangement, few data is available about the prognostic impact, the predictive value for different treatments, and the genetic heterogeneity of ROS1-positive patients. 1137 patients with adenocarcinoma of the lung...
  5. Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement: results from the EUROS1 cohort.

    Journal of Clinical Oncology 33(9):992 (2015) PMID 25667280

    Approximately 1% of lung adenocarcinomas are driven by oncogenic ROS1 rearrangement. Crizotinib is a potent inhibitor of both ROS1 and ALK kinase domains. In the absence of a prospective clinical trial in Europe, we conducted a retrospective study in centers that tested for ROS1 rearrangement. E...
  6. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial.

    The Lancet Oncology 16(3):257 (2015) PMID 25704439

    Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer. We did...
  7. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial.

    The Lancet Oncology 16(3):257 (2015) PMID 25704439

    Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer. We did...
  8. MET Amplification Status in Therapy-Naïve Adeno- and Squamous Cell Carcinomas of the Lung.

    Clinical Cancer Research 21(4):907 (2015) PMID 25492085

    MET is a potential therapeutic target in lung cancer and both MET tyrosine kinase inhibitors and monoclonal antibodies have entered clinical trials. MET signaling can be activated by various mechanisms, including gene amplification. In this study, we aimed to investigate MET amplification status...
  9. MET Amplification Status in Therapy-Naïve Adeno- and Squamous Cell Carcinomas of the Lung.

    Clinical Cancer Research 21(4):907 (2015) PMID 25492085

    MET is a potential therapeutic target in lung cancer and both MET tyrosine kinase inhibitors and monoclonal antibodies have entered clinical trials. MET signaling can be activated by various mechanisms, including gene amplification. In this study, we aimed to investigate MET amplification status...
  10. Management of crizotinib therapy for ALK-rearranged non-small cell lung carcinoma: An expert consensus

    Lung Cancer 87(2):89 (2015) PMID 25576294

    • Crizotinib is a standard of care for ALK-positive lung cancer. • Crizotinib-associated AEs are mostly mild to moderate in severity. ...
  11. Management of crizotinib therapy for ALK-rearranged non-small cell lung carcinoma: an expert consensus.

    Lung Cancer 87(2):89 (2015) PMID 25576294

    Within 4 years of the discovery of anaplastic lymphoma kinase (ALK) rearrangements in non-small cell lung cancer (NSCLC), the ALK inhibitor crizotinib gained US and European approval for the treatment of advanced ALK-positive NSCLC. This was due to the striking response data observed with crizot...
  12. PD-L1 expression in small cell neuroendocrine carcinomas.

    European Journal of Cancer 51(3):421 (2015) PMID 25582496

    Small cell lung cancer and extrapulmonary small cell carcinomas are the most aggressive type of neuroendocrine carcinomas. Clinical treatment relies on conventional chemotherapy and radiotherapy; relapses are frequent. The PD-1/PD-L1/PD-L2 pathway is a major target of anti-tumour immunotherapy. ...
  13. PIK3CA mutations in non-small cell lung cancer (NSCLC): genetic heterogeneity, prognostic impact and incidence of prior malignancies.

    Oncotarget 6(2):1315 (2015) PMID 25473901 PMCID PMC4359235

    Somatic mutations of the PIK3CA gene have been described in non-small cell lung cancer (NSCLC), but limited data is available on their biological relevance. This study was performed to characterize PIK3CA-mutated NSCLC clinically and genetically. Tumor tissue collected consecutively from 1144 NS...
  14. PIK3CA mutations in non-small cell lung cancer (NSCLC): Genetic heterogeneity, prognostic impact and incidence of prior malignancies.

    Oncotarget 6(2):1315 (2015) PMID 25473901

    Somatic mutations of the PIK3CA gene have been described in non-small cell lung cancer (NSCLC), but limited data is available on their biological relevance. This study was performed to characterize PIK3CA-mutated NSCLC clinically and genetically. Tumor tissue collected consecutively from 1144 NS...
  15. Modeling tumor dynamics and overall survival in advanced non-small-cell lung cancer treated with erlotinib.

    Journal of Thoracic Oncology 10(1):84 (2015) PMID 25226426

    Pharmacostatistical models can quantify different relationships and improve decision making in personalized medicine and drug development. Our objectives were to develop models describing non-small-cell lung cancer (NSCLC) dynamics during first-line treatment with erlotinib, and survival of the ...
  16. Modeling tumor dynamics and overall survival in advanced non-small-cell lung cancer treated with erlotinib.

    Journal of Thoracic Oncology 10(1):84 (2015) PMID 25226426

    Pharmacostatistical models can quantify different relationships and improve decision making in personalized medicine and drug development. Our objectives were to develop models describing non-small-cell lung cancer (NSCLC) dynamics during first-line treatment with erlotinib, and survival of the ...
  17. Identification of novel fusion genes in lung cancer using breakpoint assembly of transcriptome sequencing data.

    Genome biology 16(1):7 (2015) PMID 25650807 PMCID PMC4300615

    Genomic translocation events frequently underlie cancer development through generation of gene fusions with oncogenic properties. Identification of such fusion transcripts by transcriptome sequencing might help to discover new potential therapeutic targets. We developed TRUP (Tumor-specimen suit...
  18. Identification of novel fusion genes in lung cancer using breakpoint assembly of transcriptome sequencing data.

    Genome biology 16(1):7 (2015) PMID 25650807 PMCID PMC4300615

    Genomic translocation events frequently underlie cancer development through generation of gene fusions with oncogenic properties. Identification of such fusion transcripts by transcriptome sequencing might help to discover new potential therapeutic targets. We developed TRUP (Tumor-specimen suit...
  19. Rationale for co-targeting IGF-1R and ALK in ALK fusion-positive lung cancer.

    Nature Medicine 20(9):1027 (2014) PMID 25173427 PMCID PMC4159407

    Crizotinib, a selective tyrosine kinase inhibitor (TKI), shows marked activity in patients whose lung cancers harbor fusions in the gene encoding anaplastic lymphoma receptor tyrosine kinase (ALK), but its efficacy is limited by variable primary responses and acquired resistance. In work arising...
  20. Rationale for co-targeting IGF-1R and ALK in ALK fusion-positive lung cancer.

    Nature Medicine 20(9):1027 (2014) PMID 25173427 PMCID PMC4159407

    Crizotinib, a selective tyrosine kinase inhibitor (TKI), shows marked activity in patients whose lung cancers harbor fusions in the gene encoding anaplastic lymphoma receptor tyrosine kinase (ALK), but its efficacy is limited by variable primary responses and acquired resistance. In work arising...