The General Hospital Corporation

Dana-farber-cancer Institute Inc.

Wyeth

Daphne Winifred Bell

Daniel Arie Haber

Raffaella Sordella

Jeffrey E Settleman

Pasi Antero Janne

Matthew Meyerson

Thomas J Lynch

William R Sellers

Juan Guillermo Paez

Bruce E Johnson

Bruce E Johnston

Sridhar Krishna Rabindran

Nadia G Godin-Heymann

Eunice L Kwak

Daniel Haber

Disclosed herein are methods and reagents for determining the responsiveness of cancer to an epidermal growth factor receptor (EGFR) targeting treatment. The detection of these mutations will allow for the administration of gefitinib, erlotinib and other tyrosine kinase inhibitors to those patients most likely to respond to the drug.

Method to determine responsiveness of cancer to epidermal growth factor receptor targeting treatments

The present invention is directed to methods for the treatment of gefitinib and/or erlotinib resistant cancer. An individual with cancer is monitored for cancer progression following treatment with gefitinib and/or erlotinib. Progression of the cancer is indicative that the cancer is resistant to gefitinib and/or erlotinib. Once progression of cancer is noted, the subject is administered a pharmaceutical composition comprising an irreversible epidermal growth factor receptor (EGFR) inhibitor. In preferred embodiments, the irreversible EGFR inhibitor is EKB-569, HKI-272 and HKI-357.

Method for treating gefitinib resistant cancer

The present invention is directed to methods for the treatment of gefitinib and/or erlotinib resistant cancer. An individual with cancer is monitored for cancer progression following treatment with gefitinib and/or erlotinib. Progression of the cancer is indicative that the cancer is resistant to gefitinib and/or erlotinib. Once progression of cancer is noted, the subject is administered a pharmaceutical composition comprising an irreversible epidermal growth factor receptor (EGFR) inhibitor. In preferred embodiments, the irreversible EGFR inhibitor is EKB 569, HKI-272 and HKI-357.

The present invention is directed to a method for determining the responsiveness of cancer to an epidermal growth factor receptor (EGFR) treatment. In a preferred embodiment, the presence of at least one variance in the kinase domain of the erbB1 gene confers sensitivity to the tyrosine kinase inhibitor gefitinib. Thus, a diagnostic assay for these mutations will allow for the administration of gefitinib, erlotinib and other tyrosine kinase inhibitors to those patients most likely to respond to the drug.

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Chevy Chase, MD, United States of America

Daphne Winifred Bell