Genomes and Genes
Affiliation: Yale University
- The Next Wave of EGFR Tyrosine Kinase Inhibitors Enter the ClinicKaterina Politi
Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA Section of Medical Oncology, Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT 06510, USA Electronic address
Cancer Cell 27:751-3. 2015..In tyrosine kinase inhibitor-resistant lung tumors, rociletinib and AZD9291 are highly active when T790M is present and modestly active when T790M is absent. ..
- Perfect ALKemy: optimizing the use of ALK-directed therapies in lung cancerKaterina Politi
Departments of Pathology and Medicine Section of Medical Oncology, Yale University School of Medicine and Yale Cancer Center, New Haven, Connecticut
Clin Cancer Res 20:5576-8. 2014..Different mutants exhibit differential sensitivity to ALK inhibitors. Matching the mutational profile of the tumor with the appropriate ALK inhibitor is likely to be important to maximize benefit for patients...
- Two sides of the same coin: EGFR exon 19 deletions and insertions in lung cancerKaterina Politi
Yale University School of Medicine, New Haven, CT, USA
Clin Cancer Res 18:1490-2. 2012..The finding that exon 19 insertion mutations are also sensitive to this class of drugs suggests that testing for these mutations should be done and that these patients will benefit from treatment with tyrosine kinase inhibitors...
- How genetically engineered mouse tumor models provide insights into human cancersKaterina Politi
Memorial Sloan Kettering Cancer Center, New York, NY, USA
J Clin Oncol 29:2273-81. 2011..Alternatives to GEMMs, such as chemically induced or spontaneous tumor models, are not discussed in this review...
- Erlotinib resistance in mouse models of epidermal growth factor receptor-induced lung adenocarcinomaKaterina Politi
Program in Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Dis Model Mech 3:111-9. 2010..This preclinical mouse model, therefore, recapitulates the molecular changes responsible for resistance to TKIs in human tumors and holds promise for the discovery of additional mechanisms of drug resistance in lung cancer...
- Development of new mouse lung tumor models expressing EGFR T790M mutants associated with clinical resistance to kinase inhibitorsLucia Regales
Pao Lab, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America
PLoS ONE 2:e810. 2007..The EGFR T790M mutation confers acquired resistance to kinase inhibitors in human EGFR mutant lung adenocarcinoma, is occasionally detected before treatment, and may confer genetic susceptibility to lung cancer...
- Induction of BIM is essential for apoptosis triggered by EGFR kinase inhibitors in mutant EGFR-dependent lung adenocarcinomasYixuan Gong
Pao Laboratory, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America
PLoS Med 4:e294. 2007..We sought to improve understanding of this process in order to provide insight into mechanisms of sensitivity and/or resistance to tyrosine kinase inhibitors and to uncover new targets for therapy...
- HER2 amplification: a potential mechanism of acquired resistance to EGFR inhibition in EGFR-mutant lung cancers that lack the second-site EGFRT790M mutationKen Takezawa
Department of Medicine, Division of Hematology Oncology, Vanderbilt Ingram Cancer Center, Nashville, Tennessee 37232, USA
Cancer Discov 2:922-33. 2012..Collectively, these results reveal a previously unrecognized mechanism of resistance to EGFR-TKIs and provide a rationale to assess the status and possibly target HER2 in EGFR-mutant tumors with acquired resistance to EGFR-TKIs...
- Targeting the FOXO1/KLF6 axis regulates EGFR signaling and treatment responseJaya Sangodkar
Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA
J Clin Invest 122:2637-51. 2012....
- Acquired resistance of EGFR-mutant lung adenocarcinomas to afatinib plus cetuximab is associated with activation of mTORC1Valentina Pirazzoli
Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06510, USA
Cell Rep 7:999-1008. 2014....
- ERBB3-independent activation of the PI3K pathway in EGFR-mutant lung adenocarcinomasXiaoling Song
Department of Pathology and Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut
Cancer Res 75:1035-45. 2015....
- Lung adenocarcinomas induced in mice by mutant EGF receptors found in human lung cancers respond to a tyrosine kinase inhibitor or to down-regulation of the receptorsKaterina Politi
Program in Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
Genes Dev 20:1496-510. 2006..These models may be useful for developing improved therapies for patients with lung cancers bearing EGFR mutations...
- EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinibWilliam Pao
Program in Cancer Biology and Genetics and Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
Proc Natl Acad Sci U S A 101:13306-11. 2004..Collectively, these data show that adenocarcinomas from never smokers comprise a distinct subset of lung cancers, frequently containing mutations within the TK domain of EGFR that are associated with gefitinib and erlotinib sensitivity...
- Generation of drug-resistant tumors using intermittent dosing of tyrosine kinase inhibitors in mouseValentina Pirazzoli
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510
Cold Spring Harb Protoc 2014:178-81. 2014..Although this protocol is specific for this experimental system, the concepts and general design can be adapted for use with GEMMs of other cancers. ..
- Reduced NF1 expression confers resistance to EGFR inhibition in lung cancerElza C de Bruin
1Signal Transduction and 2High Throughput Screening Laboratories, Cancer Research UK London Research Institute 3The Institute of Cancer Research, London, United Kingdom 4Yale Cancer Center, Departments of 5Medicine Medical Oncology, and 6Pathology, Yale University School of Medicine, New Haven, Connecticut 7Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 8Cancer Genetics Branch, National Human Genome Research Institute, Bethesda, Maryland 9Division of Molecular Carcinogenesis, The Netherlands Cancer Institute Departments of 10Pathology and 11Pulmonary Diseases, VU University Medical Center, Amsterdam, the Netherlands 12Pathology Service, and 13Oncology Service Hospital Universitario Marques de Valdecilla, IFIMAV, Santander, Spain
Cancer Discov 4:606-19. 2014..These findings identify a subgroup of patients with EGFR-mutant lung adenocarcinoma who might benefit from combination therapy with EGFR and MEK inhibitors...
- Oncogene cooperation in tumor maintenance and tumor recurrence in mouse mammary tumors induced by Myc and mutant KrasKatrina Podsypanina
Program in Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
Proc Natl Acad Sci U S A 105:5242-7. 2008..These results demonstrate that tumor viability is maintained by each gene in a combination of oncogenes and that targeted approaches will also benefit from combination therapies...