Bruce E. Johnson, MD
Professor of Medicine, Harvard Medical School
Office phone: 617-632-4790
Preferred contact method: office phone
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Non-small cell lung cancer, Small cell lung cancer, Genomic characterization, Mesothelioma
Area of Research
The impact of genomic changes on the targeted treatment of thoracic malignancies
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA 02215
Dr. Johnson received his MD from the University of Minnesota in 1979 and his postgraduate training at the University of Chicago and the National Cancer Institute. After serving at NCI, where he most recently headed the Lung Cancer Biology Section, he joined DFCI in 1999. He currently leads the Dana-Farber/Harvard Cancer Center Lung Cancer Program and is the Chief Clinical Research Officer at the Dana-Farber Cancer Institute.
- Member of the Association of American Physicians, 2015
- Fellow of the American Society of Clinical Oncology, 2012
- American Association for Cancer Research Team Science Award, 2010
- International Association for Study of Lung Cancer Scientific Award, 2009
- The ASCO Cancer Foundation Translational Research Professorship, 2008-2013
ResearchThe impact of genomic changes on the targeted treatment of thoracic malignancies
My research is based on my multiple responsibilities as the leader of the Lung Cancer Program at the Harvard Medical School affiliated institutions. In my past role as Director of the Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute, I have been responsible for fostering collaborative research across the clinical disciplines, integrating population and basic science into our research programs, and applying innovative therapeutic strategies into the treatment of our patients with lung cancer. I have led the Lung Cancer Program within the Dana-Farber/Harvard Cancer Center from a Program in Development to a full Program and was part of the successful Dana-Farber/ Harvard Cancer Center Grant competitive renewal in 2011 and received an exceptional rating. Under my leadership, the Lung Cancer Program has been able to increase its NIH funding 5 fold in the last 16 years. In addition, the Dana-Farber/Harvard Cancer Center Lung Cancer Program successfully renewed the Lung Cancer Specialized Program of Research Excellence Grant (SPORE) in 2008 and will submit the application in the fall 2016. My translational research is devoted to testing novel therapeutic agents for their efficacy against lung cancer and other thoracic malignancies with specific genomic changes. I provide care in our Center for patients with thoracic malignancies one day per week. I also lecture widely on my research and treatment of patients with lung cancer.
Members of our research group identified the link between mutations of the epidermal growth factor receptor and response to the epidermal growth factor receptor tyrosine kinase inhibitors, gefitinib and erlotinib. Subsequent research has now changed the paradigm of treatment for patients with non-small cell lung cancer and sensitizing mutations of the epidermal growth factor receptor so the standard of care around the world is to get treated with erlotinib or gefitinib rather than chemotherapy. I am one of the patent holders of the test and now more than 50% of all the patients with nonsquamous non-small cell lung cancer get the test.
The systematic characterization of the genomic changes in lung cancer has now identified multiple changes that can lead to treatment with approved targeted agents (gefitinib and erlotinib) or enrollment onto ongoing investigation studies. These include EGFR, KRAS, HER2, BRAF, and PIK3CA mutations as well as the ALK and ROS1 rearrangements. I worked with members of our research group to set up systematic genomic characterization of nearly all of our advanced non-small cell lung cancer patients for EGFR, KRAS, HER2, BRAF, PI3KA mutations, ALK and ROS1 rearrangements, plus HER2 and MET amplification. We now characterize these genomic changes in 30-50 patients per month, track the results, are working toward placing them in the medical record, and preferentially steering these patients into appropriate genomically based protocols. It is our goal to treat a quarter of our patients with non-small cell lung cancer with targeted agents.
- Johnson BE, Fischer T, Fischer B, Dunlop R, Silberman S, Kowalski MO, Sayles D, Simitrijevic S, Fletcher C, Hornick J, Salgia R, Le Chevalier TL. Phase II study of imatinib in patients with small-cell lung cancer. Clin Cancer Res 2003;9:5880-7.
- Paez G, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WJ, Johnson BE, Meyerson M. EGFR mutations in lung cancer: correlation with clinical response to gefitinib. Science 2004;304:1497-500.
- Heymach VJ, Johnson DH, Khuri FR, Safran H, Schlabach LL, Yunus F, DeVore RF III, De Porre PM, Richards HR, Jia X, Zhang S, Johnson BE. Phase II study of the farnesyl transferase inhibitor R115777 in patients with sensitive relapse small-cell lung cancer. Ann Oncol 2004;5:1187-93.
- Jänne PA, Gurubhagavatula S, Yeap BY, Lucca J, Ostler P, Skarin AT, Fidias P, Lynch TJ, Johnson BE. Outcomes of patients with advanced non-small cell lung cancer treated with gefitinib (ZD1839, 'Iressa') on an expanded access study. Lung Cancer 2004;44:221-30.
- Tracy S, Mukohara T, Hansen M, Meyerson M, Johnson BE, Janne PA. Gefitinib induces apoptosis in the EGFRL858R non-small-cell lung cancer cell line H3255. Cancer Res 2004:64;7241-4.
- Mukohara T, Engelman JA, Hanna NH, Yeap BY, Kobayashi S, Lindeman N, Halmos B, Pearlberg J,Tsuchihashi Z, Cantley LC, Johnson BE, Jnne PA. Differential effects of gefitinib and cetuximab on non-small cell lung cancers bearing epidermal growth factor receptor mutations. J Natl Cancer Inst 2005:97:1185-94.
- Mukohara T, Civiello G, Johnson BE, Jnne PA. Therapeutic targeting of multiple signaling pathways in malignant pleural mesothelioma. Oncology 2005;68:500-10.
- Eberhard DA, Johnson BE, Amler LC, Goddard AD, Heldens SL, Herbst RS, Ince WL, Jnne PA, Januario T, Johnson DH, Klein P, Miller VA, Ostland MA, Ramies DA, Sebisanovic D, Stinson JA, Zhang YR, Seshagiri S, Hillan KJ. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol 2005;23:5900-9.
- Mukohara T, Civiello G, David IJ, Taffaro ML, Christensen J. Fisher DE, Johnson BE, Janne PA. Inhibition of the met receptor in mesothelioma. Clin Cancer Res. 2005;15;11(22):8122-30.
- Janne PA, Borras AM, Yanan Kuang Y, Rogers AM, Joshi VA, Liyanage H, Lindeman N, Lee J, Halmos B, Maher EA, Distel RJ, Meyerson M, and Johnson BE. A rapid and sensitive enzymatic method for EGFR mutation screening. Clin Cancer Res 2006;12(3):751-758.
- Engelman JA, Mukohara T, Zejnullahu K, Lifshits E, Borras AM, Christopher-Michael Gale C-M, Naumov GN, Yeap BY, Jarrell E, Sun J, Tracy S, Zhao X, Heymach JV, Johnson BE, Cantley LC, and Janne PA. Allelic dilution obscures detection of a biologically significant resistance mutation in EGFR -amplified lung cancer. J Clin Invest 2006;116:2695-706.
- Jackman DM, Yeap BY, Sequist LV, Lindeman N, Holmes AJ, Joshi VA, Bell DW, Huberman MS, Halmos B, Rabin MS, Haber DA, Lynch TJ, Meyerson M, Johnson BE and Janne PA. Exon 19 Deletion Mutations of Epidermal Growth Factor Receptor Are Associated with Prolonged Survival in NonSmall Cell Lung Cancer Patients Treated with Gefitinib or Erlotinib. Clin Cancer Res 2006;12, 3908-14.
- Chute J, Taylor E, Williams J, Le PT, Kaye F, Venzon D, Johnson BE. A Metabolic Study of Patients with Lung Cancer and Hyponatremia of Malignancy. Clin Cancer Res 2006;12(3):888-896.
- Heymach JV, Johnson BE, Prager D, Csada E, Roubec J, Pesek M, Spasova I, Belani CP, Bodrogi I, Gadgeel S, Kennedy SJ, Hou J and Herbst RS. Vandetanib (ZD6474) plus docetaxel in patients with previously treated non-small cell lung cancer: Results of a randomized, placebo-controlled phase I/II study. J Clin Onc. 2007;25(27) In press.
- Jackman DM, Yeap BY, Lindeman NI, Fidias P, Rabin MS, Temel J, Skarin AT, Meyerson M, Holmes A, Borras AM, Friedlin B, Ostler PA, Lucca J, Lynch TJ, Johnson BE, and Janne PA. Phase II clinical trial of chemotherapy-nave patients > 70 years of age treated with erlotinib for advanced non-small cell lung cancer. J Clin Oncol. 2007; 25(7):760-6.
- Herbst RS, Sun Y, Eberhardt WE, Germonpré P, Saijo N, Zhou C, Wang J, Li L,Kabbinavar F, Ichinose Y, Qin S, Zhang L, Biesma B, Heymach JV, Langmuir P, Kennedy SJ, Tada H, Johnson BE. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer(ZODIAC): a double-blind, randomized, phase 3 trial. Lancet Oncol. 2010Jul;11(7):619-26.
- Cooley ME, Emmons KM, Haddad R, Wang Q, Posner M, Bueno R, Cohen TJ, Johnson BE. Patient-reported receipt of and interest in smoking-cessation interventions after a diagnosis of cancer. Cancer. 2011 Jul 1;117(13):2961-9.
- Heon S, Yeap BY, Lindeman NI, Joshi VA, Butaney M, Britt GJ, Costa DB, Rabin MS, Jackman DM, Johnson BE. The impact of initial gefitinib or erlotinib versus chemotherapy on central nervous system progression in advanced non-small cell lung cancer with EGFR mutations. Clin Cancer Res. 2012 Aug 15;18(16):4406-14.
- Papadimitrakopoulou VA, Soria JC, Jappe A, Jehl V, Klimovsky J, Johnson BE. Everolimus and erlotinib as second- or third-line therapy in patients with advanced non-small-cell lung cancer. J Thorac Oncol. 2012 Oct;7(10):1594-601.
- Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012 Sep 27;489(7417):519-25.
- Cardarella S, Ortiz TM, Joshi VA, Butaney M, Jackman DM, Kwiatkowski DJ, Yeap BY, Jänne PA, Lindeman NI, Johnson BE. The introduction of systematic genomic testing for patients with non-small-cell lung cancer. J Thorac Oncol. 2012 Dec;7(12):1767-74.
- Cardarella S, Ogino A, Nishino M, Butaney M, Shen J, Lydon C, Yeap BY, Sholl LM, Johnson BE, Jänne PA. Clinical, Pathologic, and Biologic Features Associated with BRAF Mutations in Non-Small Cell Lung Cancer. Clin Cancer Res. 2013 Aug 15;19(16):4532-40.
- Nishino M, Dahlberg SE, Cardarella S, Jackman DM, Rabin MS, Ramaiya NH, Hatabu H, Jänne PA, Johnson BE. Volumetric tumor growth in advanced non-small cell lung cancer patients with EGFR mutations during EGFR-tyrosine kinase inhibitor therapy: Developing criteria to continue therapy beyond RECIST progression. Cancer. 2013 Nov 1;119(21):3761-8.
- Johnson BE, Kabbinavar F, Fehrenbacher L, Hainsworth J, Kasubhai S, Kressel B, Lin CY, Marsland T, Patel T, Polikoff J, Rubin M, White L, Yang JC, Bowden C, Miller V. ATLAS: Randomized, Double-Blind, Placebo-Controlled, Phase IIIB Trial Comparing Bevacizumab Therapy With or Without Erlotinib, After Completion of Chemotherapy, With Bevacizumab for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2013 Nov 1;31(31):3926-34.
- Besse B, Leighl N, Bennouna J, Papadimitrakopoulou VA, Blais N, Traynor AM, Soria JC, Gogov S, Miller N, Jehl V, Johnson BE. Phase II study of everolimus-erlotinib in previously treated patients with advanced non-small-cell lung cancer. Ann Oncol. 2014 Feb;25(2):409-15.
- Besse B, Heist RS, Papadmitrakopoulou VA, Camidge DR, Beck JT, Schmid P, Mulatero C, Miller N, Dimitrijevic S, Urva S, Pylvaenaeinen I, Petrovic K, Johnson BE. A phase Ib dose-escalation study of everolimus combined with cisplatin and etoposide as first-line therapy in patients with extensive-stage small-cell lung cancer. Ann Oncol 2014 Feb;25(2):505-11.
- Kris MG*, Johnson BE,*, Berry LD, Kwiatkowski DJ, Iafrate JA, Wistuba II, Varella-Garcia M, Franklin WA, Aronson SL, Su PF, Shyr Y, Camidge DR, Sequist LV, Glisson BS, Khuri FR, MD, Garon EB, Pao W, Rudin C, Schiller J, Haura EB, Socinski M, Shirai K, Chen H, Giaccone G, Ladanyi M, Kugler K, Minna JD, Bunn PA. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014 May 21;311(19):1998-2006.*Designates co-first authors
- Dahlberg SE, Shapiro GI, Clark JW, Johnson BE. Evaluation of statistical designs in phase I expansion cohorts: the Dana-Farber/Harvard Cancer Center experience. J Natl Cancer Inst. 2014 Jun 24;106(7).
- Kabbinavar F, Fehrenbacher L, Hainsworth J, Kasubhai S, Kressel B, Marsland T, Patel T, Rubin M, White L, Yang JC, Klughammer B, Colburn D, Miller V, Johnson BE. Biomarker analyses from a randomized, placebo-controlled, phase IIIb trial comparing bevacizumab with or without erlotinib as maintenance therapy for the treatment of advanced non-small-cell lung cancer (ATLAS). J Thorac Oncol. 2014 Sep;9(9):1411-7
- Jackman, David M., MD
- Gandhi, Leena, MD, PhD
- Ortiz, Taylor, MD
- Heon, Stephanie, MD