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'Smart drug' targets new mutation, dramatically shrinks aggressive sarcoma and lung cancer
Date:10/27/2010

BOSTON--A new oral drug caused dramatic shrinkage of a patient's rare, aggressive form of soft-tissue cancer that was driven by an abnormally activated protein, physician-scientists from Dana-Farber Cancer Institute report in the Oct. 28 issue of the New England Journal of Medicine.

A second patient who had a similar tumor that was not fueled by the mutant protein, called ALK (named for the first disease in which it was found, anaplastic lymphoma kinase), failed to respond to the drug, said the researchers, confirming the inhibitor's specificity for the abnormal protein. The findings also highlight the value of "personalized medicine" gene-testing strategies to predict the best drug treatment for an individual's particular, genetically defined cancer.

The patient described in the NEJM Brief Report is a 44-year-old man diagnosed in 2007 with inflammatory myofibroblastic tumor (IMT), a type of sarcoma that typically develops in the chest or abdomen in children and young adults.

In approximately half the cases of IMT, ALK is fused to a different protein in the patients' cancer cells, spurring cancer development. The patient had been treated with standard chemotherapy drugs followed by the targeted compound Gleevec, but the cancer returned in the form of multiple tumors.

James Butrynski, MD and Geoffrey Shapiro, MD, PhD, Dana-Farber oncologists and the first and senior authors of the report, respectively, offered the patient participation in a Phase 1 trial of an experimental drug, crizotinib, which blocks ALK activity, as well as that of another oncogene, MET, that is abnormally activated in a number of cancers.

Crizotinib treatment shrank the tumors by more than 50 percent technically called a "partial response." After several months of crizotinib, in December 2008, some of the tumors became resistant to the drug and started growing again. These tumors, as well as tumors still responsive to crizotinib, were
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Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
Source:Eurekalert  

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'Smart drug' targets new mutation, dramatically shrinks aggressive sarcoma and lung cancer
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