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

removed surgically. Crizotinib was resumed after the surgery, and the patient remains without evidence of disease as of September 2010, according to the investigators.

The activity of crizotinib goes beyond this rare sarcoma. The current report accompanies a paper in the same journal describing striking activity of crizotinib in a group of patients with non-small cell lung cancers (NSCLC) containing the abnormal ALK protein. Researchers from Massachusetts General Hospital, Dana-Farber/Brigham and Women's Cancer Center, and other hospitals gave crizotinib to 82 patients after standard drugs failed to halt the tumors' growth. As part of the personalized medicine effort ongoing in the Dana-Farber/Brigham and Women's Cancer Center Thoracic Oncology Program, patients with abnormal ALK were identified for the trial, underscoring the importance of tumor profiling to match drug with patient.

Results showed that 47 patients had tumor shrinkage (complete disappearance in one patient) and the cancer stopped growing in 27 patients. The ALK rearrangements are found in a small subset, about 5 percent, of patients with NSCLC, but scientists are searching for other cancers that may also be susceptible to the ALK inhibitor.

Shapiro noted that even highly successful targeted drugs like crizotinib are vulnerable to tumors' developing resistance against them. In fact, the IMT patient's tumors that developed resistance to crizotinib and were removed surgically have been studied by one of the reports co-authors, Pasi Janne, MD, PhD, also of Dana-Farber. In a paper appearing simultaneously in Cancer Research, Janne and his colleagues have identified a secondary mutation in ALK in the patient's tumor that conferred resistance to crizotinib. Furthermore, in work recently published by Janne, Shapiro and their Dana-Farber colleague, Kwok-Kin Wong, MD, PhD, the abnormal ALK proteins, including the protein with the secondary mutation that was resistant to crizotinib,
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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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