How chronic obstructive pulmonary disease increases risk of lung cancer
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.
"We saw that tumor growth in the hypoxic environment which mimics that of COPD conditions including chronic bronchitis and emphysema is due to signaling by HIF-2a. This HIF-2a in turn activates cancer growth promoting mechanisms including VEGF and the EGFR ligand, TGFa, which are growth factors involved in stimulating cell proliferation and the development of new blood vessels," Miller says.
Likewise, just as tumors that arise in hypoxic conditions do so through turning on pathways that lead to the over-production of VEGF and TGFa, so too are these tumors especially susceptible to cancer therapies that block these growth factors. Sure enough, animal models given the drug vandetanib a combined VEGFR/EGFR inhibitor failed to develop cancer under hypoxic conditions.
"Chemoprevention hasn't been done successfully for lung cancer," Miller says, "but this approach of VEGF/EGFR inhibitors for patients with COPD and extreme lung cancer risk may be something that should be explored further."
Miller imagines the next step is a review of patient records to discover if COPD lung cancer patients who happened to be treated with VEGF/EGFR inhibitors, in fact, had better tumor response than patients with normal lung function and similar tumors.
"Right now it's not a treatment," Miller says, "but it's an exciting line of inquiry."
Provided by University of Colorado Denver
- Early COPD detection could help lung cancer diagnosis Nov 16, 2011 | not rated yet | 0
- The right combination: Overcoming drug resistance in cancer Jun 01, 2012 | not rated yet | 0
- The link between TB and a gene mutation that causes lung cancer Jan 18, 2012 | not rated yet | 0
- EGFR gene signature predicts non-small cell lung cancer prognosis Jan 13, 2010 | not rated yet | 0
- SBRT provides better outcomes than surgery for cancer patients with common lung disease Feb 16, 2012 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
How can there be a term called "intestinal metaplasia" of stomach
17 hours ago Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
- More from Physics Forums - Medical Sciences
More news stories
The gap between life expectancy in patients with a mental illness and the general population has widened since 1985 and efforts to reduce this gap should focus on improving physical health, suggest researchers in a paper ...
Cancer 5 hours ago | not rated yet | 0
By studying the roles two proteins, thrombospondin-1 and prosaposin, play in discouraging cancer metastasis, a trans-Atlantic research team has identified a five-amino acid fragment of prosaposin that significantly reduces ...
Cancer 6 hours ago | not rated yet | 0
A novel transcriptome-based classification of colon cancer that improves the current disease stratification based on clinicopathological variables and common DNA markers is presented in a study published in PLOS Medicine this w ...
Cancer 6 hours ago | not rated yet | 0
A study of veterans at high risk for developing lung cancer shows that low-dose computed tomography (LDCT) can be highly effective in helping clinicians spot tiny lung nodules which, in a small number of patients, may indicate ...
Cancer 8 hours ago | not rated yet | 0
An attack on glioblastoma brain tumor cells that uses a modified poliovirus is showing encouraging results in an early study to establish the proper dose level, researchers at Duke Cancer Institute report.
Cancer 10 hours ago | not rated yet | 0
(Medical Xpress)—Native peoples in regions where cameras are uncommon sometimes react with caution when their picture is taken. The fear that something must have been stolen from them to create the photo ...
12 hours ago | 4.2 / 5 (5) | 0 |
(Medical Xpress)—Despite spending billions of dollars on research and development, drug companies have been unable to come up with effective treatments for dementia and Alzheimer's Disease (AD). Now, A. ...
10 hours ago | 4.9 / 5 (9) | 0 |
Activating an enzyme known to play a role in the anti-aging benefits of calorie restriction delays the loss of brain cells and preserves cognitive function in mice, according to a study published in the May ...
6 hours ago | 5 / 5 (3) | 0 |
An experimental sleeping pill from US drug company Merck is effective at helping people fall and stay asleep, according to reviewers at the US Food and Drug Administration, which could soon approve the new drug.
5 hours ago | 3 / 5 (2) | 0
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.
12 hours ago | 4.4 / 5 (5) | 0 |
A drug commonly used to treat depression and anxiety may improve a stress-related heart condition in people with stable coronary heart disease, according to researchers at Duke Medicine.
7 hours ago | not rated yet | 0 |