Researcher Profile
Pasi A. Janne, MD, PhD
Medical Oncologist
Associate Professor of Medicine, Harvard Medical School
Center/Program
Department
Medical Oncology/Solid Tumor Oncology
Interest
Lung cancer, mesothelioma
Area of Research
Impact of Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer
Contact Information
Pasi A. Janne, MD, PhDDana-Farber Cancer Institute
44 Binney Street
D820B
Boston, MA 02115
Office phone: (617) 632-6036
Fax: (617) 632-7683
E-mail: pjanne@partners.org
Preferred contact method: office phone
Research
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.
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.
Select Publications
- Eberhard DA, Johnson BE, Amler LC, Goddard AD, Heldens SL, Herbst RS, Ince WL, Jänne 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 K-ras 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.
- Engelman JA, Jänne PA, Murmel C, Pearlberg J, Mukohara T, Fleet C, Cichowski K, Johnson BE, Cantley LC. ErbB-3 mediates PI3-K activity in gefitinib-sensitive non-small cell lung cancer cell lines. Proc Natl Acad Sci U S A 2005;102:3788-93.
- Greulich H, Chen TH, Feng W, Jänne PA, Alvarez JV, Bulmer SE, Zappaterra M, Frank DA, Hahn WC, Sellers WR, Meyerson M. Oncogenic transformation by inhibitor-sensitive and resistant EGFR mutants. PLoS Med 2005;2:e313.
- Kobayashi S, Boggon TJ, Dayaram T, Jänne PA, Kocher O, Meyerson M, Johnson BE, Eck MJ, Tenen DG, Halmos B. Emergence of a drug resistance mutation in the epidermal growth factor receptor gene in gefitinib-responsive non small cell lung cancer. New Eng J Med 2005;352:786-92.
- Mukohara T, Civiello G, Davis IJ, Taffaro ML, Christensen J, Fisher DE, Johnson BE, Jänne PA. Inhibition of the Met receptor in mesothelioma. Clin Cancer Res 2005;15:11:8122-30.
- Mukohara T, Civiello G, Johnson BE, Jänne PA. Therapeutic targeting of multiple signaling pathways in malignant pleural mesothelioma. Oncology 2005;68:500-10.
- Mukohara T, Engelman JA, Hanna NH, Yeap BY, Kobayashi S, Lindeman N, Halmos B, Pearlberg J, Tsuchihashi Z, Cantley LC, Tenen DG, Johnson BE, Jänne PA. Differential effects of gefitinib and cetuximab on EGFR mutant non-small cell lung cancers. J Natl Cancer Inst 2005;97:1185-94.
- Paez JG, Jänne 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 WR, Johnson BE, Meyerson M. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004;304:1497-500.
- Tracy S, Mukohara T, Hansen M, Meyerson M, Johnson BE, Jänne PA. Gefitinib induces apoptosis in the EGFRL858R non-small cell lung cancer cell line H3255. Cancer Res 2004;64:241-4.
