- A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells
Edgar R Wood
Department of Computational, Analytical and Structural Sciences, GlaxoSmithKline, Inc, Research Triangle Park, North Carolina 27709, USA
Cancer Res 64:6652-9. 2004
..The differences in the off-rates of these drugs and the ability of GW572016 to inhibit ErbB-2 can be explained by the enzyme-inhibitor structures...
- Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib
Thomas J Lynch
Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston 02129, USA
N Engl J Med 350:2129-39. 2004
..However, about 10 percent of patients have a rapid and often dramatic clinical response. The molecular mechanisms underlying sensitivity to gefitinib are unknown...
- Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma
Tony S Mok
State Key Laboratory in Oncology in South China, Sir YK Pao Centre for Cancer, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong
N Engl J Med 361:947-57. 2009
..Previous, uncontrolled studies have suggested that first-line treatment with gefitinib would be efficacious in selected patients with non-small-cell lung cancer...
- EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy
J Guillermo Paez
Departments of Medical Oncology and Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA
Science 304:1497-500. 2004
..These results suggest that EGFR mutations may predict sensitivity to gefitinib...
- Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR
Miyagi Cancer Center, Miyagi, Japan
N Engl J Med 362:2380-8. 2010
- MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling
Jeffrey A Engelman
Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA
Science 316:1039-43. 2007
..Thus, we propose that MET amplification may promote drug resistance in other ERBB-driven cancers as well...
- Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial
Department of Thoracic Surgery, Aichi Cancer Center Hospital, Chikusa ku, Nagoya, Japan
Lancet Oncol 11:121-8. 2010
..However, whether gefitinib is better than standard platinum doublet chemotherapy in patients selected by EGFR mutation is uncertain...
- EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib
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...
- Erlotinib in previously treated non-small-cell lung cancer
Frances A Shepherd
Department of Medical Oncology, University Health Network, Princess Margaret Hospital Site, University of Toronto, Canada
N Engl J Med 353:123-32. 2005
- Screening for epidermal growth factor receptor mutations in lung cancer
Catalan Institute of Oncology and Autonomous University of Barcelona, Hospital Germans Trias i Pujol, Barcelona, Spain
N Engl J Med 361:958-67. 2009
..We evaluated the feasibility of large-scale screening for EGFR mutations in such patients and analyzed the association between the mutations and the outcome of erlotinib treatment...
- EGFR mutation and resistance of non-small-cell lung cancer to gefitinib
Division of Hematology Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
N Engl J Med 352:786-92. 2005
..Structural modeling and biochemical studies showed that this second mutation led to gefitinib resistance...
- Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain
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...
- Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group
Malcolm J Moore
Division of Medical Oncology, Princess Margaret Hospital, Toronto, Canada
J Clin Oncol 25:1960-6. 2007
..We studied the effects of adding the HER1/EGFR-targeted agent erlotinib to gemcitabine in patients with unresectable, locally advanced, or metastatic pancreatic cancer...
- Lapatinib plus capecitabine for HER2-positive advanced breast cancer
Charles E Geyer
Allegheny Cancer Center, Allegheny General Hospital, Pittsburgh, PA 15212, USA
N Engl J Med 355:2733-43. 2006
..In this trial, we compared lapatinib plus capecitabine with capecitabine alone in such patients...
- MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib
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...
- Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
Lancet 379:633-40. 2012
..We argue that the two anti-HER2 agents given together would be better than single-agent therapy...
- The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP
Cai Hong Yun
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 105:2070-5. 2008
- Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer)
Medical Oncology, Christie Hospital NHS Trust, Manchester M20 4BX, UK
Lancet 366:1527-37. 2005
..This placebo-controlled phase III study investigated the effect on survival of gefitinib as second-line or third-line treatment for patients with locally advanced or metastatic non-small-cell lung cancer...
- Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study
Department of Medical Oncology, Ospedale Civile di Livorno, Livorno, Italy
Lancet Oncol 11:521-9. 2010
- Understanding resistance to EGFR inhibitors-impact on future treatment strategies
Deric L Wheeler
Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison, WI 53705, USA
Nat Rev Clin Oncol 7:493-507. 2010
..A greater understanding of the mechanisms that lead to EGFR resistance may provide valuable insights to help design new strategies that will enhance the impact of this promising class of inhibitors for the treatment of cancer...
- Cediranib with mFOLFOX6 versus bevacizumab with mFOLFOX6 as first-line treatment for patients with advanced colorectal cancer: a double-blind, randomized phase III study (HORIZON III)
Hans Joachim Schmoll
Department of Internal Medicine IV, Hematology and Oncology, University Clinic Halle Saale, Martin Luther University Halle Wittenberg, Ernst Grube Str 40, 06120 Halle, Germany
J Clin Oncol 30:3588-95. 2012
- KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib
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...
- Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial
Edward S Kim
The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Lancet 372:1809-18. 2008
..We compared gefitinib with docetaxel in patients with locally advanced or metastatic non-small-cell lung cancer who had been pretreated with platinum-based chemotherapy...
- Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors
A F Gazdar
Hamon Center for Therapeutic Oncology Research and Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
Oncogene 28:S24-31. 2009
..Various second-generation EGFR TKIs are currently being evaluated and may have the potential to overcome T790M-mediated resistance by virtue of their irreversible inhibition of the receptor TK domain...
- Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer
Royal Marsden Hospital, London, United Kingdom
J Clin Oncol 27:5538-46. 2009
- BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models
Department of Medical Oncology, Dana Farber Cancer Institute, MA, USA
Oncogene 27:4702-11. 2008
..These findings encourage further testing of BIBW2992 in lung cancer patients harboring EGFR or HER2 oncogenes...
- Cardiovascular safety with linagliptin in patients with type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a phase 3 programme
Odd Erik Johansen
Boehringer Ingelheim, Asker, Norway
Cardiovasc Diabetol 11:3. 2012
..This study investigated the cardiovascular (CV) safety profile of the dipeptidyl peptidase (DPP)-4 inhibitor linagliptin versus comparator treatments...
- TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer
Roy S Herbst
University of Texas M D Anderson Cancer Center, Houston, USA
J Clin Oncol 23:5892-9. 2005
..Erlotinib was combined with chemotherapy to determine if it could improve the outcome of patients with NSCLC...
- First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations
Lecia V Sequist
Massachusetts General Hospital Cancer Center, 32 Fruit St, Yawkey Suite 7B, Boston, MA 02114, USA
J Clin Oncol 26:2442-9. 2008
..The multicenter iTARGET trial prospectively examined first-line gefitinib in advanced NSCLC patients harboring EGFR mutations and explored the significance of EGFR mutation subtypes and TKI resistance mechanisms...
- AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity
Program in Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Cancer Cell 19:58-71. 2011
..Consistent with this model, we find that, in tumors in which AKT suppresses HER3 expression, combined inhibition of AKT and HER kinase activity is more effective than either alone...
- Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial
Zentrum fur Pneumologie und Thoraxchirurgie, Krankenhaus D LVA, Germany
J Clin Oncol 25:1545-52. 2007
- PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib
Jeffrey A Engelman
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA
Cancer Res 67:11924-32. 2007
..These preclinical evaluations support further clinical development of PF00299804 for cancers with mutations and/or amplifications of ERBB family members...
- Efficacy and safety of linagliptin in persons with type 2 diabetes inadequately controlled by a combination of metformin and sulphonylurea: a 24-week randomized study
D R Owens
University Hospital Llandough, Cardiff, UK
Diabet Med 28:1352-61. 2011
..0-10.0%)] by metformin and sulphonylurea combination treatment...
- Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity
Cai Hong Yun
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, MA 02115, USA
Cancer Cell 11:217-27. 2007
..Strikingly, direct binding measurements show that gefitinib binds 20-fold more tightly to the L858R mutant than to the wild-type enzyme...
- Genetic heterogeneity of the epidermal growth factor receptor in non-small cell lung cancer cell lines revealed by a rapid and sensitive detection system, the peptide nucleic acid-locked nucleic acid PCR clamp
Department of Respiratory Medicine, Saitama Medical School, Moroyama machi, Iruma gun, Saitama, Japan
Cancer Res 65:7276-82. 2005
..Genetic heterogeneity of EGFR suggests that the EGFR gene is unstable in established cancers and the heterogeneity may explain variable clinical responses of lung cancers to gefitinib...
- Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial
Roy S Herbst
Department of Thoracic Head and Neck Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
Lancet 377:1846-54. 2011
- Randomized study of Lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer
Kimberly L Blackwell
Duke University Medical Center, Durham, NC 27701, USA
J Clin Oncol 28:1124-30. 2010
..EGF104900 compared the activity of lapatinib alone or in combination with trastuzumab in patients with ErbB2-positive, trastuzumab-refractory metastatic breast cancer (MBC)...
- A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses
University of Leeds, Leeds, England, UK
Breast Cancer Res Treat 112:533-43. 2008
..Updated efficacy and initial biomarker results from this trial are reported...
- Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer
Samuel A Wells
Dept of Surgery, Washington University School of Medicine, Box 8109, 660 S Euclid Ave, St Louis, MO 63110, USA
J Clin Oncol 28:767-72. 2010
..These results demonstrate that vandetanib may provide an effective therapeutic option in patients with advanced hereditary MTC, a rare disease for which there has been no effective therapy...
- Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial
Jean Yves Douillard
M D Anderson Cancer Center, Thoracic Head and Neck Medical Oncology, Box 432, 1515 Holcombe Blvd, Houston, TX 77401, USA
J Clin Oncol 28:744-52. 2010
- Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer
The Breast Center, Baylor College of Medicine, Houston, TX 77030, USA
J Natl Cancer Inst 96:926-35. 2004
..We used a breast cancer model system with high expression of AIB1 and HER2 to investigate the possible mechanisms underlying this resistance...
- Epithelial versus mesenchymal phenotype determines in vitro sensitivity and predicts clinical activity of erlotinib in lung cancer patients
Robert L Yauch
Department of Molecular Diagnostics, Genentech, Inc, South San Francisco, California 94080, USA
Clin Cancer Res 11:8686-98. 2005
..These data support a potential role for EMT as a determinant of EGFR activity in NSCLC tumor cells and E-cadherin expression as a novel biomarker predicting clinical activity of the EGFR inhibitor erlotinib in NSCLC patients...
- Epithelial to mesenchymal transition derived from repeated exposure to gefitinib determines the sensitivity to EGFR inhibitors in A549, a non-small cell lung cancer cell line
Jin Kyung Rho
Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Science, Seoul 139 706, Republic of Korea
Lung Cancer 63:219-26. 2009
..Conversely, this was reversed through the removal of TGF-beta1. In conclusion, induction of EMT may contribute to the decreased efficacy of therapy in primary and acquired resistance to gefitinib...
- Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition
Departments of Translational Research and Oncology Research, OSI Pharmaceuticals, Inc, Farmingdale, NY 11735, USA
Cancer Res 65:9455-62. 2005
..These data suggest that EMT may be a general biological switch rendering non-small cell lung tumors sensitive or insensitive to EGFR inhibition...
- Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study
M R Taskinen
Department of Medicine, Helsinki University Central Hospital, Finland
Diabetes Obes Metab 13:65-74. 2011
..To evaluate the efficacy and safety of the potent and selective dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin administered as add-on therapy to metformin in patients with type 2 diabetes with inadequate glycaemic control...
- Epithelial to mesenchymal transition in an epidermal growth factor receptor-mutant lung cancer cell line with acquired resistance to erlotinib
Department of Thoracic Surgery, Aichi Cancer Center Hospital, Chikusa ku, Nagoya, Japan
J Thorac Oncol 6:1152-61. 2011
..However, recent clinical studies revealed that gefitinib or erlotinib are highly effective in the treatment of non-small cell lung cancer with EGFR mutations...
- Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer
Nancy U Lin
Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
Clin Cancer Res 15:1452-9. 2009
..The current study was done to further evaluate the CNS activity of lapatinib. The study was later amended to allow patients who progressed on lapatinib the option of receiving lapatinib plus capecitabine...
- Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2
Roy S Herbst
Department of Thoracic Head and Neck Medical Oncology, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Unit 432, Houston, TX 77030, USA
J Clin Oncol 22:785-94. 2004
..This phase III, randomized, placebo-controlled, double-blind trial evaluated gefitinib plus paclitaxel and carboplatin in chemotherapy-naive patients with advanced NSCLC...
- Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma with epidermal growth factor receptor-activating mutations
Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan
Cancer Res 68:9479-87. 2008
..Therefore, inhibition of HGF-MET signaling may be a considerable strategy for more successful treatment with gefitinib...
- Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 1
Vrije Universiteit Medical Center, Department of Oncology, De Boelelaan 1117, 1081 Amsterdam, The Netherlands
J Clin Oncol 22:777-84. 2004
..Gefitinib has demonstrated encouraging efficacy in advanced NSCLC in phase II trials in pretreated patients, and a phase I trial of gefitinib in combination with gemcitabine and cisplatin showed favorable tolerability...
- AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer
Stephen R Wedge
Cancer Bioscience, AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom
Cancer Res 65:4389-400. 2005
..AZD2171 is being developed clinically as a once-daily oral therapy for the treatment of cancer...
- Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib
Eunice L Kwak
Center for Molecular Therapeutics, Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
Proc Natl Acad Sci U S A 102:7665-70. 2005
..Our findings suggest that one of these, HKI-272, may prove highly effective in the treatment of EGFR-mutant NSCLCs, including tumors that have become resistant to gefitinib or erlotinib...
- Transcriptional and posttranslational up-regulation of HER3 (ErbB3) compensates for inhibition of the HER2 tyrosine kinase
Joan T Garrett
Department of Medicine, Breast Cancer Research Program, Vanderbilt Ingram Cancer Center, and Vanderbilt University Institute of Imaging Sciences, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
Proc Natl Acad Sci U S A 108:5021-6. 2011
..They also suggest that therapeutic inhibitors of HER3 should be used in combination with HER2 inhibitors and PI3K pathway inhibitors in patients with HER2- and PI3K-dependent cancers...
- Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial
HELIOS Klinikum, Berlin Buch, Berlin, Germany
Lancet Oncol 13:135-44. 2012
..We compared the efficacy and safety of the addition of lapatinib versus trastuzumab to anthracycline-taxane-based neoadjuvant chemotherapy...
- A phase I dose escalation study of BIBW 2992, an irreversible dual inhibitor of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) tyrosine kinase in a 2-week on, 2-week off schedule in patients with advanced solid tumours
F A L M Eskens
Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands
Br J Cancer 98:80-5. 2008
..No partial or complete responses were observed, stable disease lasting more than four cycles was seen in seven patients. The recommended dose for studies with BIBW 2992 for 14 days followed by 14 days off medication is 70 mg OD...
- Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer
Medical Oncology Program, Medical Oncology Department, Vall d Hebron University Hospital and Research Institute, Barcelona 08035, Spain
J Natl Cancer Inst 99:628-38. 2007
- Prospective phase II study of gefitinib for chemotherapy-naive patients with advanced non-small-cell lung cancer with epidermal growth factor receptor gene mutations
Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging, and Cancer, Tohoku University, 4 1, Seiryomachi, Aoba ku, Sendai 980 8575, Japan
J Clin Oncol 24:3340-6. 2006
..This study was undertaken to investigate the efficacy and the feasibility of gefitinib for chemotherapy-naïve patients with advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations...
- PTEN loss contributes to erlotinib resistance in EGFR-mutant lung cancer by activation of Akt and EGFR
Martin L Sos
Max Planck Institute for Neurological Research with Klaus Joachim Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Köln, Germany
Cancer Res 69:3256-61. 2009
..These results suggest a novel resistance mechanism in EGFR-mutant NSCLC involving PTEN loss...
- Phase I trial of the irreversible EGFR and HER2 kinase inhibitor BIBW 2992 in patients with advanced solid tumors
Timothy A Yap
Drug Development Unit, The Royal Marsden National Health Service Foundation Trust, and the Institute of Cancer Research, Sutton, Surrey, United Kingdom
J Clin Oncol 28:3965-72. 2010
..A phase I study of continuous once-daily oral BIBW 2992 was conducted to determine safety, maximum-tolerated dose, pharmacokinetics (PK), food effect, and preliminary antitumor efficacy...
- 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...
- Effect of linagliptin monotherapy on glycaemic control and markers of β-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial
S Del Prato
Department of Endocrinology and Metabolism, Section of Metabolic Diseases, University of Pisa, Pisa, Italy
Diabetes Obes Metab 13:258-67. 2011
- Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer
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...
- Erlotinib and bevacizumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck: a phase I/II study
Ezra E W Cohen
Section of Hematology Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA University of Chicago Cancer Research Center, Chicago, IL, USA
Lancet Oncol 10:247-57. 2009
..In this multi-institutional phase I/II study we combined an EGFR inhibitor, erlotinib, with an anti-VEGF antibody, bevacizumab...
- Exon 19 deletion mutations of epidermal growth factor receptor are associated with prolonged survival in non-small cell lung cancer patients treated with gefitinib or erlotinib
David M Jackman
Lowe Center of Thoracic Oncology, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
Clin Cancer Res 12:3908-14. 2006
..Our study explored the relationship between the two most common types of somatic EGFR mutations, exon 19 deletions and the L858R point mutation, and outcomes of patients following treatment with gefitinib or erlotinib...
- Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL
Department of Translational Research, GlaxoSmithKline, King of Prussia, Pennsylvania, USA
Cancer Res 69:6871-8. 2009
- Analysis of epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer and acquired resistance to gefitinib
Department of Thoracic Surgery, Aichi Cancer Center Hospital, 1 1 Kanokoden, Chikusa ku, Nagoya 464 8681, Japan
Clin Cancer Res 12:5764-9. 2006
..Part of this "acquired resistance" is attributable to a secondary mutation resulting in threonine to methionine at codon 790 (T790M) of EGFR...
- Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence
Department of Thoracic Surgery, Aichi Cancer Center Hospital, 1 1 Kanokoden, Chikusa ku, Nagoya 464 8681, Japan
J Clin Oncol 23:2513-20. 2005
..To evaluate the relationship between mutations of the epidermal growth factor receptor (EGFR) gene and the effectiveness of gefitinib treatment in patients with recurrent lung cancer after pulmonary resection...
- Knockdown of oncogenic KRAS in non-small cell lung cancers suppresses tumor growth and sensitizes tumor cells to targeted therapy
Hamon Center for Therapeutic Oncology Research, Simmons Cancer Center, Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, USA
Mol Cancer Ther 10:336-46. 2011
..Our findings suggest that targeting oncogenic KRAS by itself will not be sufficient treatment, but may offer possibilities of combining anti-KRAS strategies with other targeted drugs...
- Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer
Eric Van Cutsem
University Hospital Gasthuisberg Leuven, Digestive Oncology Unit, Herestraat 49, B 3000 Leuven, Belgium
J Clin Oncol 27:2231-7. 2009
..Phase II results for bevacizumab plus gemcitabine provided the rationale for a phase III trial of gemcitabine-erlotinib plus bevacizumab or placebo...
- Effect of renal impairment on the pharmacokinetics of the dipeptidyl peptidase-4 inhibitor linagliptin(*)
Boehringer Ingelheim Pharma GmbH and Co KG, Ingelheim, Germany
Diabetes Obes Metab 13:939-46. 2011
- Chemogenomic profiling provides insights into the limited activity of irreversible EGFR Inhibitors in tumor cells expressing the T790M EGFR resistance mutation
Martin L Sos
Max Planck Institute for Neurological Research with Klaus Joachim Zülch Laboratories of the Max Planck Society, Center of Integrated Oncology and Department I of Internal Medicine, University of Koln, Cologne, Germany
Cancer Res 70:868-74. 2010
- Efficacy and safety of initial combination therapy with linagliptin and pioglitazone in patients with inadequately controlled type 2 diabetes: a randomized, double-blind, placebo-controlled study
Endocrinology and Diabetes Service, IDIBAPS, CIBERDEM, Hospital Clinic Villarroel, Barcelona, Spain
Diabetes Obes Metab 13:653-61. 2011
- Cediranib plus FOLFOX/CAPOX versus placebo plus FOLFOX/CAPOX in patients with previously untreated metastatic colorectal cancer: a randomized, double-blind, phase III study (HORIZON II)
Paulo M Hoff
FACP, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de Sao Paulo, Av Dr Arnaldo 251, Sao Paulo, Brazil
J Clin Oncol 30:3596-603. 2012
- ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy
Alan E Wakeling
Department of Cancer and Infection Research, AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom
Cancer Res 62:5749-54. 2002
..These studies indicate the potential utility of ZD1839 in the treatment of many human tumors and indicate that continuous once-a-day p.o. dosing might be a suitable therapeutic regimen...
- Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]
Fourth Department of Internal Medicine, Kinki University School of Medicine, 377 2 Ohnohigashi Osakasayama, Osaka 589, Japan
J Clin Oncol 21:2237-46. 2003
- Dual-agent molecular targeting of the epidermal growth factor receptor (EGFR): combining anti-EGFR antibody with tyrosine kinase inhibitor
Department of Human Oncology, University of Wisconsin School of Medicine and Comprehensive Cancer Center, 600 Highland Avenue, Madison, WI 53792 0600, USA
Cancer Res 64:5355-62. 2004
..This approach suggests potential new strategies to maximize effective target inhibition, which may improve the therapeutic ratio for anti-EGFR-targeted therapies in developing clinical trials...
- Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 6307, USA
J Clin Invest 118:2609-19. 2008
..Moreover, combined therapeutic inhibition of EGFR and IGFIR may abrogate this acquired mechanism of drug resistance and is thus worthy of prospective clinical investigation...
- Loss of phosphatase and tensin homolog or phosphoinositol-3 kinase activation and response to trastuzumab or lapatinib in human epidermal growth factor receptor 2-overexpressing locally advanced breast cancers
Lester and Sue Smith Breast Center, Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA
J Clin Oncol 29:166-73. 2011
..Understanding of the cellular response to HER2-targeted therapies is needed to tailor treatments and to identify patients less likely to benefit...
- Phase III trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel consolidation in inoperable stage III non-small-cell lung cancer: SWOG S0023
University of Kansas Medical Center, Kansas City, KS 66160, USA
J Clin Oncol 26:2450-6. 2008
..Early clinical studies with gefitinib showed promising efficacy and mild toxicity in patients with advanced non-small-cell lung cancer (NSCLC). Thus, gefitinib was an ideal agent to evaluate in a maintenance setting in stage III disease...
- Targeting the epidermal growth factor receptor in non-small cell lung cancer cells: the effect of combining RNA interference with tyrosine kinase inhibitors or cetuximab
Laboratory of Medical and Molecular Oncology and Department of Medical Oncology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium
BMC Med 10:28. 2012
- Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial
Mark G Kris
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, NY 10021, USA
JAMA 290:2149-58. 2003
- 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...
- BIM mediates EGFR tyrosine kinase inhibitor-induced apoptosis in lung cancers with oncogenic EGFR mutations
Daniel B Costa
Division of Hematology Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
PLoS Med 4:1669-79; discussion 1680. 2007
..The objective of this study was to identify the mechanism of EGFR TKI-induced apoptosis and secondary resistant mutations that affect this process...
- Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck [corrected]
J Simon W Stewart
Charing Cross Hospital, London, UK
J Clin Oncol 27:1864-71. 2009
..To compare survival in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) treated with gefitinib 250 or 500 mg/day or standard methotrexate...
- Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial
Roy S Herbst
Department of Thoracic Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 432, Houston, TX 77030 4009, USA
Lancet Oncol 11:619-26. 2010
..These results supported investigation of the combination in this larger, definitive phase 3 trial (ZODIAC)...
- Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235
Pieter J A Eichhorn
Medical Oncology Program, Vall d Hebron Institut de Oncologia, Barcelona, Spain
Cancer Res 68:9221-30. 2008
..Our data show that deregulation of the PI3K pathway, either through loss-of-function mutations in PTEN or dominant activating mutations in PIK3CA, leads to lapatinib resistance, which can be effectively reversed by NVP-BEZ235...
- Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas
Howard A Burris
The Sarah Cannon Research Institute, 250 25th Avenue N, Suite 110, Nashville, TN 37203, USA
J Clin Oncol 23:5305-13. 2005
- Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer: final survival analysis of a phase III randomized trial
University of Leeds, Leeds, UK
Oncologist 15:924-34. 2010
..Here, we report final analyses of overall survival...
- Acquired resistance to epidermal growth factor receptor kinase inhibitors associated with a novel T854A mutation in a patient with EGFR-mutant lung adenocarcinoma
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...
- Predictors of survival in patients with bone metastasis of lung cancer
Department of Orthopaedic Surgery, Aichi Cancer Center, 1 1 Kanokoden, Chikusa ku, Nagoya, Japan
Clin Orthop Relat Res 466:729-36. 2008
..The data preliminarily suggest treatment with an epithelial growth factor receptor inhibitor may improve survival after bone metastasis...
- Intermittent erlotinib in combination with pemetrexed: phase I schedules designed to achieve pharmacodynamic separation
Angela M Davies
University of California Davis Cancer Center, Sacramento, California, USA
J Thorac Oncol 4:862-8. 2009
..Pharmacodynamic separation by intermittent delivery of epidermal growth factor receptor tyrosine kinase inhibitors with chemotherapy may increase efficacy by overcoming hypothesized antagonism...
- Chemotherapy-induced epidermal growth factor receptor activation determines response to combined gefitinib/chemotherapy treatment in non-small cell lung cancer cells
Sandra Van Schaeybroeck
Department of Oncology, Centre for Cancer Research and Cell Biology, Queen s University Belfast, University Floor, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, Northern Ireland, United Kingdom
Mol Cancer Ther 5:1154-65. 2006
..These novel findings suggest that modulation of EGFR activity following drug treatment determines response to gefitinib in combination with chemotherapy in NSCLC cells...
- Epidermal growth factor receptor mutations and their correlation with gefitinib therapy in patients with non-small cell lung cancer: a meta-analysis based on updated individual patient data from six medical centers in mainland China
Yi long Wu
Lung Cancer Research Institute and Cancer Center, Guangdong Provincial People s Hospital, Guangzhou, China
J Thorac Oncol 2:430-9. 2007
..We investigated the relevance of demographic characteristics and EGFR mutations, correlations between the efficacy of gefitinib and EGFR mutations in NSCLC, and to identify individuals who would likely benefit from gefitinib...
- Gefitinib and the modulation of the signaling pathways downstream of epidermal growth factor receptor in human liver cancer cells
Jun Ichi Okano
Second Department of Internal Medicine, Tottori University School of Medicine, 36 1 Nishi cho, Yonago 683 8504, Japan
J Gastroenterol 41:166-76. 2006
..We examined whether abrogation of the TGF-alpha/EGFR signaling pathway with a selective EGFR tyrosine kinase inhibitor, gefitinib, could inhibit the proliferation of human hepatocellular carcinoma (HCC) cells...
- Discovery of 7-(4-(3-ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDc-101) as a potent multi-acting HDAC, EGFR, and HER2 inhibitor for the treatment of cancer
Curis Inc, 45 Moulton Street, Cambridge, Massachusetts 02138, USA
J Med Chem 53:2000-9. 2010
- Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors
Tumor Biology Center, MR Development and Application Center, Albert Ludwigs University, Freiburg, Germany
J Clin Oncol 25:3045-54. 2007
..This phase I study was designed to evaluate the safety and tolerability of increasing doses of AZD2171, with additional assessments of pharmacokinetics, pharmacodynamics, and efficacy...
- Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib
Department of Preventive Services, Kyoto University School of Public Health, Kyoto, Japan
J Clin Oncol 24:2549-56. 2006
..We examined the prevalence of and risk factors for gefitinib-induced ILD associated with practical use of the drug in Japanese with non-small-cell lung cancer (NSCLC)...
- A "vascular normalization index" as potential mechanistic biomarker to predict survival after a single dose of cediranib in recurrent glioblastoma patients
A Gregory Sorensen
A A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA 02114, USA
Cancer Res 69:5296-300. 2009
..54; P = 0.004) and progression-free survival (rho = 0.6; P = 0.001). The vascular normalization index described here should be validated in randomized clinical trials...
- Interstitial lung disease in Japanese patients with lung cancer: a cohort and nested case-control study
Nippon Medical School, Tokyo, Japan
Am J Respir Crit Care Med 177:1348-57. 2008
..Interstitial lung disease (ILD) occurs in Japanese patients with non-small cell lung cancer (NSCLC) receiving gefitinib...
- Erlotinib induces cell cycle arrest and apoptosis in hepatocellular cancer cells and enhances chemosensitivity towards cytostatics
Gastroenterology Infectious Diseases Rheumatology, Medical Clinic I, Charite Universitatsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany
J Hepatol 43:661-9. 2005
..Several reports indicate that EGFRs are expressed frequently in HCC, most likely contributing to the aggressive growth characteristics of these tumors...
- Gefitinib and chemotherapy combination studies in five novel human non small cell lung cancer xenografts. Evidence linking EGFR signaling to gefitinib antitumor response
Jean Gabriel Judde
Institut Curie, Section de Recherche, Paris, France
Int J Cancer 120:1579-90. 2007
..The data indicate that the antitumor activity of gefitinib in NSCLC, alone or in combination with chemotherapy, is tumor-dependent and is influenced by downstream signaling events independent of EGFR status...