Yong Jia, Cai-Hong Yun, Eunyoung Park, Dalia Ercan, Mari Manuia, Jose Juarez, Chunxiao Xu, Kevin Rhee, Ting Chen, Haikuo Zhang, Sangeetha Palakurthi, Jaebong Jang, Gerald Lelais, Michael DiDonato, Badry Bursulaya, Pierre-Yves Michellys, Robert Epple, Thomas H Marsilje, Matthew McNeill, Wenshuo Lu, Jennifer Harris, Steven Bender, Kwok-Kin Wong, Pasi A Jänne, Michael J Eck
The epidermal growth factor receptor (EGFR)-directed tyrosine kinase inhibitors (TKIs) gefitinib, erlotinib and afatinib are approved treatments for non-small cell lung cancers harbouring activating mutations in the EGFR kinase, but resistance arises rapidly, most frequently owing to the secondary T790M mutation within the ATP site of the receptor. Recently developed mutant-selective irreversible inhibitors are highly active against the T790M mutant, but their efficacy can be compromised by acquired mutation of C797, the cysteine residue with which they form a key covalent bond...
June 2, 2016: Nature