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

in patients with lung cancer. They then showed that PF-06463922 inhibited the growth of tumors harboring three of the crizotinib-resistant ALK mutants, including the most resistant ALK mutant, G1202R, in mice.

Further analysis indicated that PF-06463922 readily entered the brains of mice, rats, and dogs. In mice, levels of PF-06463922 in the brain were 20-30 percent of levels of PF-06463922 in the blood. This is potentially clinically relevant because a significant number of lung cancer patients will develop brain metastasis during the course of their disease, according to Smeal, although he noted that it will be important to see if these results in animals hold true in humans.

Smeal and colleagues also found that PF-06463922 potently inhibited the protein ROS1, a close relative of ALK recently implicated in a number of cancer types, including some lung and brain cancers. Further, PF-06463922 had antitumor effects in two mouse models of cancers driven by ROS1 gene abnormalities, leading the researchers to suggest that PF-06463922 has potential as a treatment for this subgroup of cancers, in addition to its promise as a new treatment for ALK-driven cancers.


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Contact: Lauren Riley
lauren.riley@aacr.org
215-446-7155
American Association for Cancer Research
Source:Eurekalert

Page: 1 2

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