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Targeted investigational therapy potential to overcome crizotinib resistance in lung cancers
Date:10/20/2013

BOSTON PF-06463922, an investigational drug being developed by Pfizer Inc., has the potential to become a new treatment option for patients who have lung cancer harboring abnormalities in the ALK gene, according to preclinical results presented here at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Oct. 19-23.

About 3 to 5 percent of lung cancers harbor ALK gene abnormalities. The drug crizotinib (Xalkori), which blocks ALK protein kinase activity, was approved in August 2011 by the U.S. Food and Drug Administration for the treatment of patients who have these lung cancers. Although robust responses to crizotinib are observed for lung cancers harboring ALK gene abnormalities, the majority eventually become resistant to the effects of the drug. In many cases, resistance arises because of genetic mutations in ALK.

"Resistance to targeted therapies such as crizotinib is a major challenge when treating patients with cancer," said Tod Smeal, Ph.D., associate research fellow in the Oncology Research Unit at Pfizer Inc. in San Diego, Calif. "Our goal is to take advantage of everything we have learned about designing drugs that target kinases like ALK and the ways in which lung cancers become resistant to crizotinib to develop the best next-generation ALK inhibitor we can.

"Our preclinical studies suggest that we are making progress toward achieving our goal: PF-06463922 has potent ALK-inhibiting activity, it is capable of inhibiting all the crizotinib-resistant ALK mutants so far detected in patients, and it can efficiently access the brain. We are excited about these preclinical results and very hopeful that they will translate into meaningful responses in the clinic."

After carefully designing PF-06463922, Smeal and colleagues first showed in cell assays that it potently inhibited the activity of ALK and all eight of the mutant forms of ALK known to cause resistance to crizotinib
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Contact: Lauren Riley
lauren.riley@aacr.org
215-446-7155
American Association for Cancer Research
Source:Eurekalert

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