Memorial Sloan Kettering Cancer Center

Sloan-kettering Institute for Cancer Research

Harold E Varmus

Katerina Politi

William Pao

Vincent Miller

Alexander Chucholowski

Hakim Djaballah

Mohan Santhanam Thiruvazhi

David Shum

Romel Somwar

Mohan Santhanam Thiruvahi

The present invention is directed to pyridazinone compounds of formula (I) and furan compounds of formula (II), pharmaceutical compositions of compounds of formula (I) and (II), kits containing these compounds, methods of syntheses, and a method of treatment of a proliferative disease in a subject by administration of a therapeutically effective amount of a compound of formulae (I) or (II). Both classes of compounds were identified through screening of a collection of small molecule libraries. 

Substituted pyridazines as EGFR and/or KRAS inhibitors

Development of acquired resistance to the therapeutic effects of an epidermal growth factor (EGFR) tyrosine kinase inhibitor in a patient that is suffering from a cancer is predicted by:

Methods and compositions for detecting a drug resistant EGFR mutant

Polymerase chain reaction primers and methods directed to detecting the EGFR mutant C&#x2192;T at the position corresponding to base 2369 of EGFR cDNA. The invention provides a PCR primer that hybridizes under suitable PCR conditions to a polynucleotide sequence 5' in each respective strand to a mutation of an EGFR gene that encodes a substitution of threonine by methionine at position 790 of the EGFR polypeptide. The invention also provides a PCR primer hybridizes to a sequence that includes a mutant T at the position corresponding to base 2369 of EGFR cDNA but not to a second EGFR polynucleotide containing a wild type C. The invention provides several methods and kits for detecting a mutant epidermal growth factor receptor (EGFR) gene in a sample comprising probing the sample with a means for selectively detecting a nucleotide sequence comprising a mutant T at the position corresponding to base 2369 of EGFR cDNA, and identifying that the base at said position is T. These methods and kits are also useful to predict resistance to the therapeutic effects of gefitinib or erlotinib in a subject suffering from or suspected of having a cancer.

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New York, NY, United States of America

Harold E Varmus