Hypoxic lung environment increases HIF-2a tumor growth signaling

Published on July 25, 2012 at 12:57 AM · No Comments

In addition to the well-known risk factor of smoking, chronic obstructive pulmonary disease (COPD) increases lung cancer risk.

A University of Colorado Cancer Center study published in the journal Cancer Prevention Research details one novel mechanism of this risk: long-term oxygen depletion stimulates signals that promote tumor growth. In addition, this early study - performed in animal models - shows that tumors fueled by these COPD-induced signals may be especially susceptible to prevention or perhaps even treatment with drugs that turn off these same signals, namely VEGFR-2 and EGFR inhibitors.

"At least in animal models, this study shows an important pathway activated in lung tumors arising in poorly oxygenated regions of the lung that isn't activated to nearly the same degree in other lung cancers," says York Miller, MD, investigator at the CU Cancer Center and professor in the Department of Pulmonary Sciences and Critical Care Medicine at the University of Colorado School of Medicine and Denver Veterans Affairs Medical Center, the paper's senior author.

"There are probably other mechanisms driving lung cancer in COPD as well - for example, inflammation is also very likely playing in - but this paper shows that the hypoxic sensing pathway is specifically activated in these COPD lung cancer models and that this sensing pathway is to a large degree driving tumor growth," Miller says.

Specifically, his study used animal models designed to develop cancer, which the group placed in high altitude chambers set to mimic the chronic oxygen depletion of found in parts of the lung affected by COPD. Mice in the hypoxic condition developed larger tumors than mice given normal oxygen, but, according to Miller, what was especially striking is the reason for this tumor growth.

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