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:2/23/2017)... ... , ... The 89th Academy Awards will be celebrated this weekend, which means ... Bunkum Award. We invite you to enjoy our 11th annual tongue-in-cheek “salute” to the ... Center for American Progress (CAP), for its report, Lessons From State Performance on NAEP: ...
(Date:2/23/2017)... Chapel Hill, NC (PRWEB) , ... February 23, 2017 , ... ... the Platinum Sponsor for ACPA’s 74th Annual Meeting. KLS is a longtime supporter ... in 2017 as an exhibitor and Platinum Sponsor," said Dr. Bob Havlik, 2017 ACPA ...
(Date:2/23/2017)... ... February 23, 2017 , ... Rosica Communications, ... relations, content marketing, social media management, corporate communications, SEO and cause marketing, is ... and in nearby New Hampshire, Massachusetts and Canada, Rosica will focus on expanding ...
(Date:2/23/2017)... ... ... Dr. David Mahon leads Siena Dental, a comprehensive dental practice located at 10075 ... Patient Rated Henderson Dentist by Find Local Doctors earlier this year. ... who have earned high ratings and superior patient reviews from multiple credible sources. , ...
(Date:2/23/2017)... ... , ... Current Meditation , a new meditation concept ... U.S. starting this spring. Current Meditation focuses on “meditation for the modern world,” ... will be the first meditation concept in the U.S. offering franchising opportunities, setting ...
Breaking Medicine News(10 mins):
(Date:2/23/2017)... Im Rahmen seiner Schlüsselwachstumsstrategie arbeitet die Guian ... Provinz Guizhou, 2017 mit dem Angebot von Anreize schaffenden Strategien ... einer eingebetteten Hightech-Schlüsselindustrie. Foto - http://mma.prnewswire.com/media/471342/First_CRH__CHina_Railway_High_Speed__Train_Enters_Guian.jpg ... ... ...
(Date:2/23/2017)... New York , February 23, 2017 ... implications arising from increasing caseload for varicose veins in ... across the globe are prompting the adoption of endovenous ... study on global endovenous laser therapy market, ... towards aftereffects of lifestyle choices and consequences of obesity ...
(Date:2/23/2017)... -- As National Nutrition Month approaches, USA Medical is providing ... people live healthier lives by providing discounts on ... all 50 states including:  Texas Prescription Assistance Program ... Assistance Program . USA Medical also shares ... nutritious eating habits: Limit ...
Breaking Medicine Technology: