William Pao

Summary

Affiliation: Vanderbilt University
Country: USA

Publications

  1. pmc Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer
    William Pao
    Department of Medicine, Vanderbilt Ingram Cancer Center, 2220 Pierce Avenue, 777 Preston Research Building, Nashville, Tennessee 37232 6307, USA
    Nat Rev Cancer 10:760-74. 2010
  2. doi request reprint Genetically informed lung cancer medicine
    William Pao
    Vanderbilt Ingram Cancer Center, Department of Medicine Division of Hematology Oncology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Pathol 223:230-40. 2011
  3. pmc High expression levels of total IGF-1R and sensitivity of NSCLC cells in vitro to an anti-IGF-1R antibody (R1507)
    Yixuan Gong
    Pao Laboratory, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America
    PLoS ONE 4:e7273. 2009
  4. pmc Targeted next-generation sequencing of DNA regions proximal to a conserved GXGXXG signaling motif enables systematic discovery of tyrosine kinase fusions in cancer
    Juliann Chmielecki
    Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10021, USA
    Nucleic Acids Res 38:6985-96. 2010
  5. pmc Routine multiplex mutational profiling of melanomas enables enrollment in genotype-driven therapeutic trials
    Christine M Lovly
    Division of Hematology Oncology, Department of Medicine, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
    PLoS ONE 7:e35309. 2012
  6. pmc Epidermal growth factor receptor tyrosine kinase inhibitor-resistant disease
    Kadoaki Ohashi
    University School of Medicine, Nashville, TN, USA
    J Clin Oncol 31:1070-80. 2013
  7. pmc New approaches to targeted therapy in lung cancer
    William Pao
    Vanderbilt Ingram Cancer Center, 2220 Pierce Avenue 777 PRB, Nashville, TN 37232, USA
    Proc Am Thorac Soc 9:72-3. 2012
  8. ncbi request reprint New driver mutations in non-small-cell lung cancer
    William Pao
    Department of Medicine, Vanderbilt Ingram Cancer Center, Nashville, TN 37232 6307, USA
    Lancet Oncol 12:175-80. 2011
  9. ncbi request reprint Integration of molecular profiling into the lung cancer clinic
    William Pao
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    Clin Cancer Res 15:5317-22. 2009
  10. pmc Dual targeting of EGFR can overcome a major drug resistance mutation in mouse models of EGFR mutant lung cancer
    Lucia Regales
    Pao Laboratory, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    J Clin Invest 119:3000-10. 2009

Detail Information

Publications80

  1. pmc Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer
    William Pao
    Department of Medicine, Vanderbilt Ingram Cancer Center, 2220 Pierce Avenue, 777 Preston Research Building, Nashville, Tennessee 37232 6307, USA
    Nat Rev Cancer 10:760-74. 2010
    ..This Review summarizes recent developments aimed at treating and ultimately curing the disease...
  2. doi request reprint Genetically informed lung cancer medicine
    William Pao
    Vanderbilt Ingram Cancer Center, Department of Medicine Division of Hematology Oncology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Pathol 223:230-40. 2011
    ..A genetically-informed approach to lung cancer medicine is rapidly becoming the standard of care worldwide and should lead to improved outcomes for patients...
  3. pmc High expression levels of total IGF-1R and sensitivity of NSCLC cells in vitro to an anti-IGF-1R antibody (R1507)
    Yixuan Gong
    Pao Laboratory, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America
    PLoS ONE 4:e7273. 2009
    ..The IGF receptor type 1 (IGF-1R) pathway is frequently deregulated in human tumors and has become a target of interest for anti-cancer therapy...
  4. pmc Targeted next-generation sequencing of DNA regions proximal to a conserved GXGXXG signaling motif enables systematic discovery of tyrosine kinase fusions in cancer
    Juliann Chmielecki
    Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10021, USA
    Nucleic Acids Res 38:6985-96. 2010
    ..This method is distinct from other similar efforts, because it focuses specifically on targets with therapeutic potential, uses only 1.5 µg of DNA, and circumvents the need for complex computational sequence analysis...
  5. pmc Routine multiplex mutational profiling of melanomas enables enrollment in genotype-driven therapeutic trials
    Christine M Lovly
    Division of Hematology Oncology, Department of Medicine, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
    PLoS ONE 7:e35309. 2012
    ....
  6. pmc Epidermal growth factor receptor tyrosine kinase inhibitor-resistant disease
    Kadoaki Ohashi
    University School of Medicine, Nashville, TN, USA
    J Clin Oncol 31:1070-80. 2013
    ..EGFR-mutant lung cancer was first described as a new clinical entity in 2004. Here, we present an update on new controversies and conclusions regarding the disease...
  7. pmc New approaches to targeted therapy in lung cancer
    William Pao
    Vanderbilt Ingram Cancer Center, 2220 Pierce Avenue 777 PRB, Nashville, TN 37232, USA
    Proc Am Thorac Soc 9:72-3. 2012
    ..Pao discussed three main topics: (1) DETECT (DNA Evaluation of Tumors for Enhanced Cancer Treatment), (2) MyCancerGenome.org (web-based decision support), and (3) DIRECT (DNA-mutation Inventory to Refine and Enhance Cancer Treatment)...
  8. ncbi request reprint New driver mutations in non-small-cell lung cancer
    William Pao
    Department of Medicine, Vanderbilt Ingram Cancer Center, Nashville, TN 37232 6307, USA
    Lancet Oncol 12:175-80. 2011
    ..The adoption of treatment tailored according to the genetic make-up of individual tumours would involve a paradigm shift, but might lead to substantial therapeutic improvements...
  9. ncbi request reprint Integration of molecular profiling into the lung cancer clinic
    William Pao
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    Clin Cancer Res 15:5317-22. 2009
    ..Implementation will facilitate realization of the promise of molecularly tailored therapy, which could lead to more effective treatments with fewer side effects...
  10. pmc Dual targeting of EGFR can overcome a major drug resistance mutation in mouse models of EGFR mutant lung cancer
    Lucia Regales
    Pao Laboratory, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    J Clin Invest 119:3000-10. 2009
    ..Moreover, this approach could serve as an important model for targeting other receptor tyrosine kinases activated in human cancers...
  11. doi request reprint Use of epidermal growth factor receptor/Kirsten rat sarcoma 2 viral oncogene homolog mutation testing to define clonal relationships among multiple lung adenocarcinomas: comparison with clinical guidelines
    Nicolas Girard
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Chest 137:46-52. 2010
    ..Here, we report on seven patients in whom epidermal growth factor receptor (EGFR) and Kirsten-rat sarcoma 2 viral oncogene homolog (KRAS) tumor mutation status was used to determine clonal relationships among multiple lung lesions...
  12. pmc Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers
    Helena A Yu
    Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Clin Cancer Res 19:2240-7. 2013
    ..Smaller series have identified various mechanisms of resistance, but systematic evaluation of a large number of patients to definitively establish the frequency of various mechanisms has not been conducted...
  13. pmc Characteristics of lung cancers harboring NRAS mutations
    Kadoaki Ohashi
    Vanderbilt Ingram Cancer Center, Department of Medicine Division of Hematology Oncology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Clin Cancer Res 19:2584-91. 2013
    ..We used preclinical models to identify targeted therapies likely to be of benefit against NRAS-mutant lung cancer cells...
  14. ncbi request reprint A phase II trial of Salirasib in patients with lung adenocarcinomas with KRAS mutations
    Gregory J Riely
    Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York City, New York, USA
    J Thorac Oncol 6:1435-7. 2011
    ..Salirasib prevents Ras membrane binding thereby blocking the function of all Ras isoforms. This phase II study determined the activity of salirasib in patients with advanced lung adenocarcinomas with KRAS mutations...
  15. pmc Acquired resistance to epidermal growth factor receptor kinase inhibitors associated with a novel T854A mutation in a patient with EGFR-mutant lung adenocarcinoma
    James Bean
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Clin Cancer Res 14:7519-25. 2008
    ..We aimed to identify additional second-site alterations associated with acquired resistance...
  16. pmc EGFR mutations in lung adenocarcinomas: clinical testing experience and relationship to EGFR gene copy number and immunohistochemical expression
    Allan R Li
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    J Mol Diagn 10:242-8. 2008
    ..Thus, these results indicate that EGFR amplification, preferentially of the mutant allele, often accompanies EGFR mutation, whereas EGFR immunohistochemical staining associates with amplification but cannot predict EGFR mutation status...
  17. doi request reprint Comprehensive histologic assessment helps to differentiate multiple lung primary nonsmall cell carcinomas from metastases
    Nicolas Girard
    Pao Lab, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Am J Surg Pathol 33:1752-64. 2009
    ..Given its high correlation with molecular characterization of such tumors, it may provide a much cheaper and faster method to address this problem...
  18. pmc Development of new mouse lung tumor models expressing EGFR T790M mutants associated with clinical resistance to kinase inhibitors
    Lucia 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...
  19. pmc EGFR-mutant lung adenocarcinomas treated first-line with the novel EGFR inhibitor, XL647, can subsequently retain moderate sensitivity to erlotinib
    Juliann Chmielecki
    Weill Cornell Graduate School of Medical Sciences, New York, New York, USA
    J Thorac Oncol 7:434-42. 2012
    ..We explored whether all EGFR TKIs similarly select for the T790M mutation using data from early clinical trials and established in vitro models of acquired resistance...
  20. ncbi request reprint Clinical course of patients with non-small cell lung cancer and epidermal growth factor receptor exon 19 and exon 21 mutations treated with gefitinib or erlotinib
    Gregory J Riely
    Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Clin Cancer Res 12:839-44. 2006
    ..We undertook this study to explore the relationship between EGFR mutation type and clinical variables, including treatment with gefitinib and erlotinib...
  21. pmc Mutational analysis of EGFR and related signaling pathway genes in lung adenocarcinomas identifies a novel somatic kinase domain mutation in FGFR4
    Jenifer L Marks
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America
    PLoS ONE 2:e426. 2007
    ..We performed mutational profiling of a large cohort of lung adenocarcinomas to uncover other potential somatic mutations in genes of this signaling pathway that could contribute to lung tumorigenesis...
  22. doi request reprint Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib
    Vincent A Miller
    Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Howard Building, Room 1012, 1275 York Ave, New York, NY 10021, USA
    J Clin Oncol 26:1472-8. 2008
    ..We conducted this phase II trial to determine the efficacy of erlotinib in patients with bronchioloalveolar carcinoma (BAC) and adenocarcinoma, BAC subtype, and to determine molecular characteristics associated with response...
  23. pmc Phase II trial of gefitinib and everolimus in advanced non-small cell lung cancer
    Katharine A Price
    Department of Medicine, Thoracic Oncology Service, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University, New York City, New York, USA
    J Thorac Oncol 5:1623-9. 2010
    ..This phase II trial assessed the efficacy of the combination of gefitinib and everolimus in patients with advanced NSCLC...
  24. ncbi request reprint Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors
    Marissa N Balak
    Human Oncology and Pathogenesis Program, Thoracic Oncology Service, Varmus Lab, Department of Pathology, Memorial Sloan Kettering Cancer Center, Weill Medical College of Cornell University, New York, New York 10021, USA
    Clin Cancer Res 12:6494-501. 2006
    ..We aimed to elucidate the frequency and nature of secondary EGFR mutations in patients with acquired resistance to TKI monotherapy...
  25. pmc Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain
    William Pao
    Program in Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    PLoS Med 2:e73. 2005
    ..Despite initial responses, patients eventually progress by unknown mechanisms of "acquired" resistance...
  26. ncbi request reprint Phase 1 trial of everolimus and gefitinib in patients with advanced nonsmall-cell lung cancer
    Daniel T Milton
    Department of Medicine, Thoracic Oncology Service, Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center and the Weill Medical College of Cornell University, New York, New York, USA
    Cancer 110:599-605. 2007
    ..A phase 1 study was conducted of the combination of everolimus, an mTOR inhibitor, and gefitinib to determine a daily dose of everolimus with gefitinib in patients with advanced nonsmall-cell lung cancer (NSCLC)...
  27. ncbi request reprint Prognostic and therapeutic implications of EGFR and KRAS mutations in resected lung adenocarcinoma
    Jenifer L Marks
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Thorac Oncol 3:111-6. 2008
    ..Whether EGFR and KRAS mutations also have an impact on survival in patients who undergo lung resection for curative intent in the absence of targeted therapy has not been established...
  28. pmc Core needle lung biopsy specimens: adequacy for EGFR and KRAS mutational analysis
    Stephen B Solomon
    Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Howard 118, New York, NY 10021, USA
    AJR Am J Roentgenol 194:266-9. 2010
    ....
  29. pmc Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor EGFR mutations
    Yelena Y Janjigian
    Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Medical College of Cornell University, New York City, New York, USA
    J Thorac Oncol 6:569-75. 2011
    ..Whether treatment with TKI improves outcomes in patients with resected lung adenocarcinoma and EGFR mutation is unknown...
  30. pmc Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1
    Kadoaki Ohashi
    Division of Hematology Oncology, Department of Medicine, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Proc Natl Acad Sci U S A 109:E2127-33. 2012
    ....
  31. pmc Analysis of genetic variants in never-smokers with lung cancer facilitated by an Internet-based blood collection protocol: a preliminary report
    Nicolas Girard
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    Clin Cancer Res 16:755-63. 2010
    ..We hypothesized that we could use the Internet to bolster the accrual of appropriate patients...
  32. doi request reprint Phase I/II trial of cetuximab and erlotinib in patients with lung adenocarcinoma and acquired resistance to erlotinib
    Yelena Y Janjigian
    Gastrointestinal and Thoracic Oncology Services, Division of Solid Tumor Oncology, Department of Medicine and Radiology, Memorial Sloan Kettering Cancer Center, Weill Medical College of Cornell University, New York, New York 10065, USA
    Clin Cancer Res 17:2521-7. 2011
    ..To evaluate the toxicity and efficacy of cetuximab and erlotinib in patients with acquired resistance to erlotinib, we conducted this phase I/II clinical trial...
  33. pmc Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer
    David Jackman
    Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA
    J Clin Oncol 28:357-60. 2010
    ..These guidelines should minimize reporting of false-positive and false-negative activity in these clinical trials and would facilitate the identification of agents that truly overcome acquired resistance to gefitinib and erlotinib...
  34. ncbi request reprint Use of cigarette-smoking history to estimate the likelihood of mutations in epidermal growth factor receptor gene exons 19 and 21 in lung adenocarcinomas
    DuyKhanh Pham
    Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    J Clin Oncol 24:1700-4. 2006
    ..Investigators have reported an association between EGFR mutations and the amount and duration of cigarette smoking, with the highest incidence of mutations seen in never smokers...
  35. pmc Somatic mutations of the Parkinson's disease-associated gene PARK2 in glioblastoma and other human malignancies
    Selvaraju Veeriah
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    Nat Genet 42:77-82. 2010
    ..These data strongly point to PARK2 as a tumor suppressor on 6q25.2-q27. Thus, PARK2, a gene that causes neuronal dysfunction when mutated in the germline, may instead contribute to oncogenesis when altered in non-neuronal somatic cells...
  36. pmc Morphologic features of adenocarcinoma of the lung predictive of response to the epidermal growth factor receptor kinase inhibitors erlotinib and gefitinib
    Maureen F Zakowski
    Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    Arch Pathol Lab Med 133:470-7. 2009
    ..A subset of lung adenocarcinomas appears preferentially sensitive to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). EGFR-activating mutations and never smoking are associated with response to TKIs...
  37. pmc Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation
    Geoffrey R Oxnard
    Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Medical College of Cornell University, New York 10065, USA
    Clin Cancer Res 17:1616-22. 2011
    ..In half of these cases, a second EGFR mutation, T790M, underlies acquired resistance. We undertook this study to examine the clinical course of patients harboring the T790M mutation following progression on TKI...
  38. pmc KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib
    William Pao
    Program in Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    PLoS Med 2:e17. 2005
    ..Lung adenocarcinomas also harbor activating mutations in the downstream GTPase, KRAS, and mutations in EGFR and KRAS appear to be mutually exclusive...
  39. pmc Maintained sensitivity to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer recurring after adjuvant erlotinib or gefitinib
    Geoffrey R Oxnard
    Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York, USA
    Clin Cancer Res 17:6322-8. 2011
    ..To better understand these results, we studied the natural history of lung cancers which recurred despite adjuvant TKI...
  40. pmc Rebiopsy of lung cancer patients with acquired resistance to EGFR inhibitors and enhanced detection of the T790M mutation using a locked nucleic acid-based assay
    Maria E Arcila
    Molecular Diagnostics Service, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Clin Cancer Res 17:1169-80. 2011
    ..Here, we sought to determine the feasibility of tumor rebiopsy and to more accurately assess the prevalence of the T790M using a highly sensitive locked nucleic acid (LNA) PCR/sequencing assay. MET amplification was also analyzed...
  41. ncbi request reprint Prospective assessment of discontinuation and reinitiation of erlotinib or gefitinib in patients with acquired resistance to erlotinib or gefitinib followed by the addition of everolimus
    Gregory J Riely
    Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    Clin Cancer Res 13:5150-5. 2007
    ..In these patients, we sought to assess changes in tumor metabolism and size after stopping and restarting erlotinib or gefitinib and to determine the effect of adding everolimus...
  42. ncbi request reprint Molecular on/off switch
    Daniel T Milton
    Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center and the Weil Medical College of Cornell University, New York, NY, USA
    J Clin Oncol 24:4940-2. 2006
  43. pmc Phase II trial of dasatinib for patients with acquired resistance to treatment with the epidermal growth factor receptor tyrosine kinase inhibitors erlotinib or gefitinib
    Melissa L Johnson
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    J Thorac Oncol 6:1128-31. 2011
    ..The SRC inhibitor dasatinib demonstrates antitumor activity in gefitinib-resistant cells lines and xenografts. Dasatinib is tolerable for patients with advanced non-small cell lung cancer, and in combination with erlotinib...
  44. doi request reprint Molecularly tailored adjuvant chemotherapy for resected non-small cell lung cancer: a time for excitement and equipoise
    Christopher G Azzoli
    Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Medical College of Cornell University, New York, New York 10021, USA
    J Thorac Oncol 3:84-93. 2008
    ..This paper will review the molecular markers which are having immediate impact on treatment decisions in routine practice, and which merit further study in the next generation of adjuvant chemotherapy trials...
  45. pmc Induction of BIM is essential for apoptosis triggered by EGFR kinase inhibitors in mutant EGFR-dependent lung adenocarcinomas
    Yixuan 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...
  46. pmc Molecular characteristics predict clinical outcomes: prospective trial correlating response to the EGFR tyrosine kinase inhibitor gefitinib with the presence of sensitizing mutations in the tyrosine binding domain of the EGFR gene
    Naiyer A Rizvi
    Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University, New York, New York 10021, USA
    Clin Cancer Res 17:3500-6. 2011
    ..To determine if tumor regression following treatment with gefitinib correlates with the presence of sensitizing mutations in epidermal growth factor receptor (EGFR)...
  47. pmc MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib
    James Bean
    Human Oncology and Pathogenesis Program, Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 104:20932-7. 2007
    ..Taken together, these data suggest that MET amplification occurs independently of EGFR(T790M) mutations and that MET may be a clinically relevant therapeutic target for some patients with acquired resistance to gefitinib or erlotinib...
  48. ncbi request reprint Molecular study of malignant gliomas treated with epidermal growth factor receptor inhibitors: tissue analysis from North American Brain Tumor Consortium Trials 01-03 and 00-01
    Andrew B Lassman
    Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Clin Cancer Res 11:7841-50. 2005
    ....
  49. pmc Optimization of dosing for EGFR-mutant non-small cell lung cancer with evolutionary cancer modeling
    Juliann Chmielecki
    Weill Cornell Graduate School of Medical Sciences, New York, NY 10021, USA
    Sci Transl Med 3:90ra59. 2011
    ..This modeling predicted alternative therapeutic strategies that could prolong the clinical benefit of TKIs against EGFR-mutant NSCLCs by delaying the development of resistance...
  50. ncbi request reprint A phase I/II study of weekly high-dose erlotinib in previously treated patients with nonsmall cell lung cancer
    Daniel T Milton
    Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center and the Weill Medical College of Cornell University, New York, New York 10021, USA
    Cancer 107:1034-41. 2006
    ..The objective of this study was to determine the tolerability and efficacy of high-dose erlotinib administered on a weekly schedule to patients with advanced nonsmall cell lung cancer (NSCLC)...
  51. pmc HER2 amplification: a potential mechanism of acquired resistance to EGFR inhibition in EGFR-mutant lung cancers that lack the second-site EGFRT790M mutation
    Ken 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...
  52. pmc Screening for germline EGFR T790M mutations through lung cancer genotyping
    Geoffrey R Oxnard
    Thoracic Oncology Service and Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    J Thorac Oncol 7:1049-52. 2012
    ..We hypothesized that patients with lung cancers found to harbor the EGFR T790M resistance mutation before treatment, an uncommon occurrence, would be likely to carry underlying germline T790M mutations...
  53. pmc "Pulsatile" high-dose weekly erlotinib for CNS metastases from EGFR mutant non-small cell lung cancer
    Christian Grommes
    Department of Neurology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
    Neuro Oncol 13:1364-9. 2011
    ..Pulsatile erlotinib can control CNS metastases from EGFR mutant lung cancer after failure of standard daily dosing. CNS disease may not harbor acquired resistance mutations that develop systemically. A prospective trial is planned...
  54. pmc Genomic and mutational profiling to assess clonal relationships between multiple non-small cell lung cancers
    Nicolas Girard
    Pao Lab, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Clin Cancer Res 15:5184-90. 2009
    ..Decisions are currently made using the Martini and Melamed criteria, which are mostly based on tumor location and histologic type. New genomic tools could improve the ability to assess tumor clonality...
  55. pmc Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas
    Sizhi Paul Gao
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Clin Invest 117:3846-56. 2007
    ..Therefore, mutant EGFR could activate the gp130/JAK/STAT3 pathway by means of IL-6 upregulation in primary human lung adenocarcinomas, making this pathway a potential target for cancer treatment...
  56. pmc Comprehensive genomic analysis reveals clinically relevant molecular distinctions between thymic carcinomas and thymomas
    Nicolas Girard
    Human Oncology and Pathogenesis Program HOPP, Weill Medical College of Cornell University, New York, New York, USA
    Clin Cancer Res 15:6790-9. 2009
    ..However, whether the underlying biology of these tumors warrants such clustering is unclear, and the optimum treatment of either entity is unknown...
  57. pmc BRAF(L597) mutations in melanoma are associated with sensitivity to MEK inhibitors
    Kimberly Brown Dahlman
    Vanderbilt Ingram Cancer Center, Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Cancer Discov 2:791-7. 2012
    ..A patient with BRAF(L597S) mutant metastatic melanoma responded significantly to treatment with the MEK inhibitor, TAK-733. Collectively, these data show clinical significance to BRAF(L597) mutations in melanoma...
  58. pmc A pilot study of volume measurement as a method of tumor response evaluation to aid biomarker development
    Binsheng Zhao
    Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    Clin Cancer Res 16:4647-53. 2010
    ....
  59. pmc Next-generation sequencing of paired tyrosine kinase inhibitor-sensitive and -resistant EGFR mutant lung cancer cell lines identifies spectrum of DNA changes associated with drug resistance
    PeiLin Jia
    Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Genome Res 23:1434-45. 2013
    ....
  60. pmc DNA-Mutation Inventory to Refine and Enhance Cancer Treatment (DIRECT): a catalog of clinically relevant cancer mutations to enable genome-directed anticancer therapy
    Paul Yeh
    Vanderbilt Ingram Cancer Center, Nashville, TN 37232, USA
    Clin Cancer Res 19:1894-901. 2013
    ....
  61. pmc Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma
    Gregory J Riely
    Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Clin Cancer Res 14:5731-4. 2008
    ..These mutations are predictive of poor prognosis in resected disease as well as resistance to treatment with erlotinib or gefitinib...
  62. ncbi request reprint Epidermal growth factor receptor mutations, small-molecule kinase inhibitors, and non-small-cell lung cancer: current knowledge and future directions
    William Pao
    Program in Cancer Biology and Genetics and the Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    J Clin Oncol 23:2556-68. 2005
    ..Here, we present current knowledge about EGFR mutations in the context of clinical trials involving gefitinib and erlotinib in NSCLC...
  63. doi request reprint KRAS mutations in non-small cell lung cancer
    Gregory J Riely
    Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Proc Am Thorac Soc 6:201-5. 2009
    ..In this review, we summarize the initial discovery of RAS mutations in NSCLC, describe work exploring associations with clinical factors and outcomes, and provide an overview of current approaches to targeting KRAS mutant NSCLC...
  64. pmc High dose weekly erlotinib achieves therapeutic concentrations in CSF and is effective in leptomeningeal metastases from epidermal growth factor receptor mutant lung cancer
    Jennifer L Clarke
    Department of Neurology and Brain Tumor Center, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
    J Neurooncol 99:283-6. 2010
    ..However, intermittent (pulsatile) high dose administration (1000-1500 mg/week) achieves a higher CSF concentration than standard dosing, and successfully controlled LM in this patient...
  65. doi request reprint Systematic screen for tyrosine kinase rearrangements identifies a novel C6orf204-PDGFRB fusion in a patient with recurrent T-ALL and an associated myeloproliferative neoplasm
    Juliann Chmielecki
    Weill Cornell Graduate School of Medical Sciences, New York, NY, USA
    Genes Chromosomes Cancer 51:54-65. 2012
    ..These data validate the ability of this targeted capture-sequencing approach to detect TK fusion events in small amounts of DNA extracted directly from patient samples...
  66. ncbi request reprint Practical management of patients with non-small-cell lung cancer treated with gefitinib
    Neelam T Shah
    Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    J Clin Oncol 23:165-74. 2005
    ..Many of the principles of management relevant to gefitinib are distinct from those with conventional cytotoxic drugs. To meet this need, we present practical guidelines on the use of gefitinib in patients with non-small-cell lung cancer...
  67. pmc Rapid polymerase chain reaction-based detection of epidermal growth factor receptor gene mutations in lung adenocarcinomas
    Qiulu Pan
    Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    J Mol Diagn 7:396-403. 2005
    ..These assays offer higher sensitivity and ease of scoring and eliminate the need for sequencing, providing a robust and accessible approach to the rapid identification of most lung cancer patients likely to respond to EGFR inhibitors...
  68. ncbi request reprint Update on epidermal growth factor receptor mutations in non-small cell lung cancer
    Gregory J Riely
    Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Clin Cancer Res 12:7232-41. 2006
    ..Although a tremendous amount of knowledge has been gained in the past 2 years, there remain a number of important epidemiologic, biological, and clinical questions...
  69. ncbi request reprint Lung adenocarcinoma: guiding EGFR-targeted therapy and beyond
    Marc Ladanyi
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Mod Pathol 21:S16-22. 2008
    ....
  70. pmc Novel MEK1 mutation identified by mutational analysis of epidermal growth factor receptor signaling pathway genes in lung adenocarcinoma
    Jenifer L Marks
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cancer Res 68:5524-8. 2008
    ..MEK1 mutants have not previously been reported in lung cancer and may provide a target for effective therapy in a small subset of patients with lung adenocarcinoma...
  71. pmc Genetic predictors of MEK dependence in non-small cell lung cancer
    Christine A Pratilas
    Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cancer Res 68:9375-83. 2008
    ....
  72. ncbi request reprint Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer
    Vincent A Miller
    Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    J Clin Oncol 22:1103-9. 2004
    ..Phase II trials suggested female sex and adenocarcinoma were associated with response. We undertook this analysis to identify additional clinical and pathologic features associated with sensitivity to gefitinib...
  73. pmc The tyrosine phosphatase PTPRD is a tumor suppressor that is frequently inactivated and mutated in glioblastoma and other human cancers
    Selvaraju Veeriah
    Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 106:9435-40. 2009
    ..PTPRD was found to dephosphorylate the oncoprotein STAT3. These results implicate PTPRD as a tumor suppressor on chromosome 9p that is involved in the development of GBMs and multiple human cancers...
  74. pmc Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors
    Christine M Lovly
    Departments of Medicine and Biostatistics, Vanderbilt University, Nashville, Tennessee, USA
    Cancer Res 71:4920-31. 2011
    ..Our findings offer preclinical proof-of-concept for use of these novel agents to improve therapeutic outcomes of patients with mutant ALK-driven malignancies...
  75. pmc 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 receptors
    Katerina 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...
  76. ncbi request reprint Defining clinically relevant molecular subsets of lung cancer
    William Pao
    Human Oncology and Pathogenesis Program, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 125, New York, NY 10021, USA
    Cancer Chemother Pharmacol 58:s11-5. 2006
    ..We are now using a variety of molecular and biological approaches to help further define molecular subsets of lung cancer that have relevance in the clinic...
  77. pmc EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib
    William 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...
  78. ncbi request reprint Combining EGFR targeted therapy with chemotherapy in pancreatic cancer: is timing important?
    Gregory J Riely
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cancer Biol Ther 4:1096-7. 2005
  79. ncbi request reprint 'Targeting' the epidermal growth factor receptor tyrosine kinase with gefitinib (Iressa) in non-small cell lung cancer (NSCLC)
    William Pao
    Department of Medicine and Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 62, New York, NY 10021, USA
    Semin Cancer Biol 14:33-40. 2004
    ..Whether EGFR is required for the maintenance of lung tumor survival is also discussed. Finally, strategies to identify predictors of response to gefitinib are explored...
  80. pmc A protein knockdown strategy to study the function of beta-catenin in tumorigenesis
    Feng Cong
    Program in Cell Biology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    BMC Mol Biol 4:10. 2003
    ..Aberrant Wnt signaling, which results from mutations of either beta-catenin or adenomatous polyposis coli (APC), renders beta-catenin resistant to degradation, and has been associated with multiple types of human cancers...