Cold Spring Harbor, NY -- One of the most tantalizing developments in anti-cancer therapy over recent years has been the advent of targeted treatments, which have proven highly effective in holding aggressive cancers at bay in certain patients, although typically only for a limited period of time.
A team led by Raffaella Sordella, Ph.D., an Assistant Professor at Cold Spring Harbor Laboratory (CSHL), today published results of a study that suggests new ways in which tumor cells develop resistance to one of the most successful targeted therapies, the small-molecule drug Tarceva (erlotinib). Since its approval by the U.S. Food and Drug Administration in 2004, Tarceva has produced dramatic, albeit impermanent, remissions in a subset of patients with notoriously difficult-to-treat cancers including non-small cell lung cancer (NSCLC) and pancreatic cancer.
Tarceva homes in on a specific area, or domain, of a very common cell-membrane receptor called EGFR, the epidermal growth-factor receptor. The drug has been shown to be effective in some NSCLC patients with specific oncogenic (cancer-promoting) mutations of EGFR. The drug molecule physically occupies a tiny pocket in the receptor structure--within an area called the tyrosine kinase domain, located just beneath the surface of the cell. This prevents the receptor from initiating a cascade of internal signals that can cause cellular growth to careen out of control, something like a switch stuck in the "on" position.
Over recent years Sordella and colleagues have focused on the question of how NSCLC tumor cells develop resistance to Tarceva. Specifically, they wanted to move beyond known explanations accounting for about half of the observed resistance. "Our colleagues in the field have already shown that secondary mutations of EGFR or amplification of a gene called c-MET are responsible for about 50% of cases of Tarceva resistance. We wanted to explain the other cases, in which the mec
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| Contact: Peter Tarr tarr@cshl.edu 516-367-8455 Cold Spring Harbor Laboratory Source:Eurekalert |
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