• Researcher Profile

    Pasi A. Jänne, MD, PhD

     
    Pasi A. Jänne, MD, PhD

    Top Doctor

     
    Director, Lowe Center for Thoracic Oncology
    Scientific Director, Belfer Institute for Applied Cancer Science
    Senior Physician


    Professor of Medicine, Harvard Medical School

    Center/Program

    Thoracic Oncology

    Office phone: 617-632-6036
    Fax: 617-582-7683
    Email: pjanne@partners.org
    Website: The Jänne Lab

    Preferred contact method: office phone

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    Research Department

    Medical Oncology/Solid Tumor Oncology

    Interests

    Lung cancer, Epidermal growth factor receptor targeted therapies, Translational medicine, Targeted therapies

    Area of Research

    Impact of Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer

    Dana-Farber Cancer Institute
    450 Brookline Avenue
    HIM 223
    Boston, MA 02215

    Biography

    Dr. Jänne received his MD and PhD from the University of Pennsylvania in 1996. He completed postgraduate training in internal medicine at Brigham and Women's Hospital and in medical oncology at DFCI in 2001. He currently works in the Lowe Center for Thoracic Oncology at DFCI. His main research interests include the study of epidermal growth factor receptor mutations in non-small cell lung cancer and their impact on the efficacy of EGFR-targeted therapeutic agents.

    Recent Awards

    • Research Excellence Award; Uniting Against Lung Cancer, 2010
    • Richard and Hinda Rosenthal Memorial Award; American Association for Cancer Research, 2010
    • Team Science Award; American Association for Cancer Research, 2010
    • Hope Now Award for Lung Cancer Research; Joan’s Legacy: The Joan Scarangello Foundation to Conquer Lung Cancer, 2007
    • George P. Canellos Award for Excellence in Clinical Investigation and Patient Care; Dana Farber Cancer Institute, 2005
    • Tisch Family Award for Outstanding Achievement in Clinical Investigation; Dana Farber Cancer Institute, 2004
    • Merit Award, American Society of Clinical Oncology, 2001

    Research

    Impact of Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer

    Laboratory-based investigations of EGFR inhibitors in NSCLC.
    Our laboratory work focuses on studying preclinical models of lung cancers, with and without epidermal growth factor receptor (EGFR) mutations. The main focus of this work is to better define the biology of EGFR and to understand how specific inhibitors of EGFR, such as erlotinib (Tarceva), gefitinib (Iressa), and cetuximab (Erbitux), exert their impact on lung cancers. In addition, studies are ongoing to understand mechanisms of resistance in these models and to develop preclinical data on ways to circumvent such mechanisms. The overall goal is to use these preclinical data to understand and better define EGFR-based treatments for patients with NSCLC.


    Translational research studies in patients with NSCLC.
    A second focus of our research is developing methods to test for genetic changes in patients' lung cancers. Recently, we demonstrated that genetic alterations (mutations) in EGFR predicted the clinical response to the EGFR inhibitor gefitinib. Thus it now becomes possible to test for these changes in patients' tumors and to make treatment decisions based on this information. Working with the translational research laboratory, we are developing a highly sensitive and specific method for identifying mutations in EGFR and other genes in lung cancer tumor specimens. This information will be incorporated into clinical treatments and clinical trials. Ultimately these studies may lead to personalized care - choosing treatment based on the genetic profile of the individual tumor.


    Clinical studies of EGFR and other kinase inhibitors.
    The goal of clinical studies is to implement the preclinical and translational research observations into treatments for patients with NSCLC. Dr. Jänne leads multiple clinical studies of EGFR inhibitors for patients with NSCLC. Since EGFR inhibitors are most effective in patients with EGFR mutations, Dr. Jänne is conducting clinical trials of such agents in newly diagnosed patients with advanced NSCLC who are most likely to have EGFR mutations. These studies will help determine whether EGFR inhibitors are better initial treatments than chemotherapy for this subset of patients with NSCLC.

    Select Publications

    • Paez, J.G., *Jänne, P.A., Lee, J.C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F.J., Lindeman, N.Boggon, T.J., Naoki, K., Sasaki, H., Fujii, Y., Eck, M.J., Sellers, W.R., Johnson, B.E., and Meyerson, M. (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science, 304 (5676):1497-1500. [*co-first author]
    • Tracy, S., Mukohara, T., Hansen, M., Meyerson, M., Johnson, B.E., and Jänne, P.A. (2004) Gefitinib induces apoptosis in the EGFRL858R Non-Small Cell Lung Cancer Cell line H3255, Cancer Res, 2004, Oct 15; 64: 7241-4.
    • Kobayashi, S., Boggon, T.J., Dayaram, T., Jänne, P.A., Kocher, O., Meyerson, M., Johnson, B.E., Eck, M.J., Tenen, D.G., and Halmos, B. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. New England Journal of Medicine; 2005; 352: 786-92.
    • Ji, H., Li, D., Chen, L., Shimamura, T., Kobayashi, S., McNamara, K., Mahmood, U., Mitchell, A., Sun,Y.,  Al-Hashem, R., Chirieac, L.R., Padera,  R., Bronson, R.T., Kim, W., Jänne, P.A., Shapiro, G.I.,  Tenen, D., Johnson, B.E., Weissleder, R., Sharpless, N.E., and Wong, K. The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR targeted therapies. Cancer Cell 2006; 9(6):485-95. 
    • Engelman, J.A., Mukohara, T., Zejnullahu, K., Lifshits, E., Borrás, A.M., Gale, C.-M., Naumov, G.N., Yeap, B.Y., Jarrell, E., Sun, J., Tracy, S., Zhao, X., Heymach, J.V., Johnson, B.E., Cantley, L.C. and Jänne, P.A. Allelic dilution obscures detection of a biologically significant resistance mutation in EGFR-amplified lung cancer. J Clin Invest 2006;116(10):2695-2706. PMCID: PMC1570180
    • Engelman, J.A., Zejnullahu, K., Mitsudomi, T., Song, Y., Hyland, C., Park, J.O., Lindeman, N., Gale, C.-M., Zhao,  X., Christensen, J., Kosaka, K., Holmes, A.J.,  Rogers, A.M., Cappuzzo, F., Mok, T., Lee, C., Johnson, B.E., Cantley,  L.C., and Jänne, P.A. MET Amplification Leads to Gefitinib Resistance by Activating ERBB3 Signaling in Lung Cancer. Science 2007; 316(5827):1039-43.
    • Engelman, J.A., Zejnullahu, K, Gale, C.-M., Lifshits, E., Gonzales, A.J., Shimamura, T.,  Zhao, F., Vincent, P.W., Naumov, G.N., Bradner, J.E., Althaus, I.W., Gandhi, L., Shapiro, G.I., Nelson, J.M., Heymach, J.V., Meyerson, M., Wong, K.-K. and Jänne, P.A. PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib. Cancer Research 2007; 67:11924-32.
    • Koivunen, J.P, Mermel, C., Zejnullahu, K., Murphy, C., Lifshits, E., Holmes, A.J., Choi, H.G., Kim, Chiang, J.D., Thomas, R., Lee, J., Richards, W.G., Sugarbaker, D.J., Ducko, C., Lindeman, N., Marcoux, J.P., Engelman, J.A., Gray, N.S., Lee, C., Matthew Meyerson, M., and Jänne, P.A.  EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin Cancer Res 2008; 14(13):4275-83.
    • Zhou, W., Ercan, D., Chen, L., Yun, C.-H., Li, D., Capelletti, M., Cortot, A.B., Chirieac, L., Lacob, R.E., Padera, R., Engen, J.R., Wong, K.-K., Eck, M.J., Gray, N.S., and Jänne, P.A. Novel mutant-selective EGFR kinase inhibitors effective against EGFR T790M. Nature 2009; 462(7276):1070-4. PMCID: PMC2879581
    • Turke, A.,B., Zejnullahu, K., Wu, Y.-L., Song, Y., Dias-Santagata, D., Lifshits, E., Toschi, L., Rogers, A., Mok, T., Sequist, L., Lindeman, N.I., Murphy, c., Akhavanfard, S., Yeap, B.Y., Xiao, Y., Capelletti, M., Iafrate, A.J., Lee, C., Christensen, J.G., Engelman, J.A., and Jänne, P.A. Pre-existence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer Cell 2010; 17(1):77-88; PMCID: PMC2980857
    • Chen, Z., Sasaki, T., Tan, X., Carretero, J., Shimamura, T., Li, D., Xu, C., Wang, Y., Adelmant,  G.O.,  Capelletti, M., Lee, H.J., Rodig, S., Borgman, C., Park, S.-I., Kim, H.R., Padera, R., Marto,   J.A. , Gray, N.S., Kung, A.L., Shapiro, G.I., Jänne, P.A*., and Wong, K.K. Inhibition of ALK,  PI3K/MEK and HSP90 in Inducible EML4-ALK-driven Murine Lung Adenocarcinoma. Cancer Research 2010; 70(23):9827-9836. [*co-corresponding author]  PMCID: PMC3043107
    • Sasaki T., Okuda K., Zheng W., Butrynski J., Capelletti M., Wang L., Gray N.S., Wilner K., Christensen J.G., Demetri G., Shapiro G.I., Rodig S.J., Eck M.J, and Jänne PA. The Neuroblastoma-Associated F1174L ALK Mutation Causes Resistance to an ALK Kinase Inhibitor in ALK-Translocated Cancers. Cancer Research. 2010;70(24):10038-10043. PMCID: PMC3045808 
    • Sasaki, T., Koivunen, J., Ogino, A., Yanagita, M., Nikiforow, S., Zheng, W., Lathan, C., Marcoux,  J.P., Du, J., Okuda, K., Capelletti, M., Shimamura, T., Ercan, D., Stumpfova, M., Xiao, Y., Weremowicz, S., Butaney, M., Heon, S., Wilner, K., Christensen, J.G., Eck, M.J., Wong, K.-K., Lindeman, N., Gray, N.S., Rodig, S.J., and Jänne, P.A. A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors. Cancer Research 2011; 71(18):6051-60. NIHMSID 337524 
    • Yonesaka, K., Zejnullahu, K., Okamoto, I., Satoh, T., Cappuzzo, F., Souglakos, J., Ercan, D., Rogers, A., Roncalli, M., Takeda, M., Fujisaka, Y., Philips, J., Shimizu, T., Maenishi, O., Cho, Y., Sun, J., Destro, A., Taira, K., Takeda, K., Okabe, T., Swanson, J., Itoh, H., Takada, M., Lifshits, E.,  Okuno, K., Engelman, J.A., Shivdasani, R.A., Nishio, K., Fukuoka, M., Varella-Garcia, M., Nakagawa, K. and Jänne, P.A. Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab. Science Translational Medicine 2011; 3(99):99ra86. NIHMSID 337522 
    • Lipson, D., Capelletti, M. Yelensky, R., Otto, G., Parker, A., Jarosz, M., Curran, J.A., Balasubramanian, S., Bloom, T., Brennan, K.W., Donahue, A.,  Downing, S.R., Frampton, G.M., Garcia, L., Juhn, F., Mitchell, K.C., White, E., White, J., Zwirko, Z., Peretz, T., Nechushtan, H., Soussan-Gutman, L., Kim, J., Sasaki, H., Kim, H.R.,  Park, S., Ercan, D., Sheehan, C.E., Ross, J.S., Cronin, M.T., Jänne, P.A.*,  and Stephens, P.J. Identification of novel ALK and RET gene fusions from colorectal and lung cancer biopsies. Nature Medicine 2012; 18(3):382-4 [*co-corresponding author]
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