Navigation Links
A new tool to confront lung cancer
Date:6/19/2014

Only 15% of patients with squamous cell lung cancer the second most common lung cancer survive five years past diagnosis. Little is understood about how the deadly disease arises, preventing development of targeted therapies that could serve as a second line of defense once standard chemotherapy regimens fail.

Published online in Cell Reports on June 19, Huntsman Cancer Institute investigators report that misregulation of two genes, sox2 and lkb1, drives squamous cell lung cancer in mice. The discovery uncovers new treatment strategies, and provides a clinically relevant mouse model in which to test them.

"This is the most exciting thing we've done," said senior author Trudy Oliver, Ph.D., an assistant professor of oncological sciences at the University of Utah and Huntsman Cancer Institute investigator. "Now that we have a model it unleashes so many questions we can ask to gain a better understanding of the disease."

By definition, tumors are groups of cells that are out of control. As a result, they acquire mutations, only some of which drive properties such as excess growth and motility - that make cells cancerous. The trick for developing targeted therapies is to distinguish the "driver" from "passenger" mutations that are merely along for the ride.

Call it guilt by association, but Oliver's team honed in on drivers of squamous cell carcinoma (SCC) of the lung by poring through documented gene abnormalities found in human SCCs. Sox2 was designated a prime candidate based on its overexpression in 60-90% of SCCs, and a frequent early appearance during tumor formation, suggesting it could be an initiator of cancer. Tumor suppressor genes were also candidates, including Lkb1, which is mutated in 5-19% of SCCs.

While disruption of either gene alone failed to trigger cancer, combining overexpression of sox2 in the lung with loss of lkb1 led to frequent development of lung SCC in mice.

"A pathologist looking under the microscope at our tumors would not know it's from the mouse," said Oliver. "They visually look like human tumors, and then when we stain them for biomarkers of the human disease, our mouse tumors light up for those markers."

Unlike most previously existing lung SCC mouse models that develop multiple tumor types, the sox2/lkb1 model generates SCC exclusively. Combine this with the fact that it was created based on patient data makes the model clinically relevant, and well poised for testing novel targeted therapies.

"Beyond lung cancer, findings from this model may have important clinical implications for other squamous or Sox2-driven malignancies such as small cell lung cancer, and brain, esophageal, and oral cancers," said Anandaroop Mukhopadhyay, Ph.D., Huntsman Cancer Institute scientist and lead author on the paper.

While there are no known drugs that directly target either Sox2 or Lkb1, there are existing therapies that interfere with biochemical pathways that are thought to be activated by these genes. What's more, the scientists found that these pathways, Jak-Stat and mTOR, were activated in tumors in the new mouse model. These findings suggest that the drugs that block these pathways, STAT3 and mTOR inhibitors, are good candidates for working as lung SCC targeted therapies.

"These are pathways that had not been previously explored for the treatment of squamous tumors because we didn't realize they were important," Oliver explained. "That gives us direction for testing the efficacy of drugs aimed at these pathways."


'/>"/>

Contact: Linda Aagard
Linda.Aagard@hci.utah.edu
801-587-7639
University of Utah Health Sciences
Source:Eurekalert  

Related medicine news :

1. Disabled shoppers confront holiday shopping barriers
2. Study Suggests Vaccine May Help Kids With Brain Cancer
3. New Stool Test Might Aid in Early Detection of Colon Cancer
4. Study reveals how cancer drug causes diabetic-like state
5. How a cancer drug leads to diabetes
6. You Survived Cancer: Now Pay Attention to Your Overall Health
7. New drug prevents spread of human prostate cancer cells
8. Eliminating the good cholesterol receptor may fight breast cancer
9. Taller, Heavier Women May Face Higher Ovarian Cancer Risk
10. Experimental Chemo Combo for Colon Cancer Disappoints
11. Veggies Like Broccoli, Cabbage May Help Fight Breast Cancer: Study
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
A new tool to confront lung cancer
(Date:5/26/2016)... ... May 26, 2016 , ... ... is happy to announce the launch of its brand equity product, Brandvantage. ... to reflect the dynamic landscape of modern consumer decision-making. The proprietary framework ...
(Date:5/26/2016)... , ... May 26, 2016 , ... Development Team of ... for FCPX. , "This new layered style transition tool will keep a consistent ... - CEO of Pixel Film Studios. , TranSweep is an all new layered ...
(Date:5/26/2016)... Beach, Florida (PRWEB) , ... May 26, 2016 , ... ... connected to the mainland by a single drawbridge, citizens formed an organization, Madeira Beach ... already congested traffic and change the small town center to a high rise urban ...
(Date:5/26/2016)... ... May 26, 2016 , ... According to the Webster’s dictionary, a ... with chemical-laden beauty products, one company is going against the norm with a line ... The rising star in the green space is proud to announce its latest retail ...
(Date:5/26/2016)... California (PRWEB) , ... May 26, 2016 , ... ... Barbara this Memorial Day weekend to host their second pop-up shop for three ... Diego fashion forward brand to the Santa Barbara community, a community full of ...
Breaking Medicine News(10 mins):
(Date:5/25/2016)... Texas , May 25, 2016 ... the issuance to it by the US Patent ... The company,s technology includes proprietary processes for electronic ... for health and wellness programs, HIPAA compliance and ... "Our technology ...
(Date:5/24/2016)... Cirujanos holandeses han puesto en marcha una ... compartir sus mejores prácticas por el mundo y tratar ... Europa, África, Asia y Estados ... combina la transmisión en vivo con mensajería instantánea y ... "Imagine un médico de Medicines sans Frontieres ...
(Date:5/24/2016)...  NxStage Medical, Inc. (Nasdaq: NXTM ), ... care, today announced that Jeffrey H. Burbank , ... schedule of investor conferences. Where applicable, a webcast of ... .   ... Friday, June 10, 2016 1:30 p.m. ET ...
Breaking Medicine Technology: