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Pasi A. Jänne, MD, PhD


Medical Oncology

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Physician

  • Director, Lowe Center for Thoracic Oncology
  • Director, Belfer Center for Applied Cancer Science
  • Senior Physician
  • Professor of Medicine, Harvard Medical School

Centers/Programs

Clinical Interests

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

Diseases Treated

  • Lung Cancer, non-small cell

Contact Information

  • Appointments877-332-4294 (new)
    617-632-6190 (established)
  • Office Phone Number617-632-6036
  • Fax617-632-5786

Bio

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 is the director of the Lowe Center for Thoracic Oncology and the Scientific Director of the Belfer Center for Applied Cancer Science. His main research interests include studying the therapeutic relevance of oncogenic alterations in lung cancer. He was one of the co-discoverers of epidermal growth factor receptor (EGFR) mutations and has led the development of therapeutic strategies for patients with EGFR mutant lung cancer.

Board Certification:

  • Internal Medicine, 1999
  • Medical Oncology, 2001

Fellowship:

  • Dana-Farber/Partners CancerCare, Hematology & Oncology

Residency:

  • Brigham and Women's Hospital, Internal Medicine

Medical School:

  • University of Pennsylvania School of Medicine

Recent Awards:

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

Location

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

 Targeted therapies in lung cancer, novel EGFR inhibitors, mechanisms of drug resistance

Laboratory-based investigations of Targeted Therapies in Lung Cancer Our laboratory work focuses on studying preclinical models of lung cancers that harbor oncogenic alterations. The main focus of our work is to understand how oncogenic alterations found in lung cancer lead to sensitivity of targeted therapies. Furthermore, we extensively study both model systems and patient derived tumors to uncover mechanisms of drug resistance. Through these studies we have been able to identify novel therapeutic strategies for patients with different genomic subtypes of lung cancer.

Preclinical and clinical development of novel EGFR directed therapies The most common mechanism (found in 60% of patients) of resistance to EGFR inhibitors is the secondary EGFR T790M mutation. The initial studies identified a second class of EGFR inhibitors, covalent or irreversible inhibitors, which could still be effective in model systems harboring EGFR T790M. We have extensively studied one such covalent inhibitor, dactominib, both in preclinical models and in lung cancer patients and despite its efficacy in preclinical models, this drug was not clinically effective in EGFR mutant lung cancer patients that had failed first generation inhibitors. One reason for this disconnect pre-clinically and clinically is that the concentrations of dacomitinib required to inhibit EGFR T790M cannot be reached in patients due to the development of on-target dose limiting toxicity (skin rash, mediated by inhibition of wild type (WT) EGFR) at much lower doses. Prompted by these clinical observations, we began working together with Dr. Nathanael Gray (who is a kinase chemist at DFCI) to tackle this problem. These studies led us to identify a previously unknown class of covalent inhibitors, irreversible pyrimidine inhibitors, which were effective EGFR inhibitors This novel chemical class of agents is both more potent than irreversible quinazolines (like dacomitinib) against EGFR T790M and is EGFR wild type sparing thus potentially improving the therapeutic window. At least 7 pharmaceutical companies have now developed clinical agents inspired by our original finding. We led the phase I clinical trial of one of these agents, osimertinib (AZD9291), which was approved by the FDA in November 2015. We continue to study this class of inhibitors and to use both laboratory and clinical studies to develop novel combination therapies.  

Clinical trials of targeted therapies in lung cancer Dr. Jänne has led multiple clinical trials of targeted therapies for patients with specific genomic subtypes of lung cancer. Many of these studies have led to either changing or improving the standard of care for patients with lung cancer. Currently, Dr. Jänne is focusing on developing combination targeted therapies and on clinical studies focusing on preventing and/delaying the emergence of drug resistance.

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