Navigation Links
Study reveals mechanism of lung-cancer drug resistance
Date:1/19/2012

  • The most common form of lung cancer inevitably develops resistance to the targeted drug gefitinib.
  • This study shows how this resistance develops.
  • The findings suggest a new strategy for treating non-small cell lung cancer.

COLUMBUS, Ohio New research published in Nature Medicine indicates that targeted drugs such as gefitinib might more effectively treat non-small cell lung cancer if they could be combined with agents that block certain microRNAs.

The study was led by investigators with the Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC James). It shows that overexpression of two genes, called MET and EGFR, causes the deregulation of six microRNAs, and that this deregulation leads to gefitinib resistance.

The findings support the development of agents that restore the levels of these microRNAs. It also offers a new strategy for treating non-small cell lung cancer (NSCLC), which is responsible for about 85 percent of the 221,000 lung-cancer cases and 157,000 deaths that occur annually in the United States.

Finally, it suggests that measuring the expression levels of certain microRNAs those controlled by the MET gene might predict which lung-cancer cases are likely to be resistant to gefitinib.

EGFR (which stands for "epidermal growth factor receptor") is frequently overexpressed in non-small cell lung cancer (NSCLC), and this leads to uncontrolled cell proliferation. Gefitinib selectively inhibits EGFR activation and triggers cancer cells to self-destruct by apoptosis. NSCLC cells inevitably develop resistance to the drug, however. This study reveals how this resistance occurs.

"Our findings suggest that gefitinib resistance that is caused by MET overexpression is at least partly due to miRNA deregulation," says principal investigator Dr. Carlo M. Croce, director of Ohio State's Human Cancer Genetics program and a member of the OSUCCC James Molecular Biology and Cancer Genetics program.

First author Michela Garofalo notes that stratifying NSCLC patients based on MET expression or the expression of miRNAs regulated by MET might allow for individualization of treatment.

"Such a strategy could improve treatment efficacy and patient quality of life by sparing patients from the side effects of treatments that are likely to fail," says Garofalo, who is a research scientist in Croce's laboratory at the OSUCCC James.

For this study, Croce, Garofalo and their colleagues used lung cancer cell lines, animal models and analysis of human NSCLC tissue. Key technical findings include the following:

  • Both EGFR and MET control miR-30b, miR30c, miR-221, and miR-222. These miRNAs are oncogenic; they inhibit pro-apoptotic genes.
  • Overexpression of the four oncogenic miRNAs rendered gefitinib-sensitive cells resistant to treatment; inhibiting the four enhanced gefitinib sensitivity and blocked NSCLC tumor growth in an animal model.
  • MET alone controls levels of miR-103 and miR-203, which have a tumor-suppressor function. Forcing their expression enhanced gefitinib sensitivity and blocked NSCLC tumor growth in an animal model.


'/>"/>
Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University Medical Center
Source:Eurekalert

Related medicine news :

1. Study finds potential key to immune suppression in cancer
2. The Pill Can Help Ease Period Pain, Study Finds
3. University of Maryland study: Headphone-distracted pedestrians face death, serious injury
4. Study reveals origins of esophageal cancer
5. Researchers study how chemicals in drugs and around us impact stem cells
6. UH Case Medical Center publishes study on novel treatment for skin lymphoma
7. Retention study identifies key factors affecting 3 generations of nurses
8. Younger Adults on Multiple Meds at Risk for Falls: Study
9. Vitamin D Wont Help Most COPD Patients: Study
10. Study suggests junk food in schools doesnt cause weight gain among children
11. Childrens Drowning Injuries, Deaths Decline: Study
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... (PRWEB) , ... June 26, 2016 , ... Pixel Film ... Pro X. , "Film editors can give their videos a whole new perspective by ... Austin - CEO of Pixel Film Studios. , ProSlice Levels contains over 30 ...
(Date:6/26/2016)... ... , ... Brent Kasmer, a legally blind and certified personal trainer is helping to develop a ... fitness app plans to fix the two major problems leading the fitness industry today:, ... type program , They don’t eliminate all the reasons people quit their exercise ...
(Date:6/25/2016)... ... 25, 2016 , ... Experts from the American Institutes for ... Meeting June 26-28, 2016, at the Hynes Convention Center in Boston. , AIR ... care planning, healthcare costs and patient and family engagement. , AIR researchers will ...
(Date:6/25/2016)... ... June 25, 2016 , ... The temporary closing of Bruton Memorial Library on June 21 due ... up a new, often overlooked aspect of head lice: the parasite’s ability to live away ... a common occurrence, but a necessary one in the event that lice have simply gotten ...
(Date:6/25/2016)... , ... June 25, 2016 , ... First Choice ... States, named Dr. Sesan Ogunleye, as the Medical Director of its new Mesquite-Samuell Farm ... Medical Director of our new Mesquite location,” said Dr. James M. Muzzarelli, Executive Medical ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... DUBLIN , June 24, 2016 ... addition of the "Structural Electronics 2015-2025: Applications, ... In-Mold Electronics, Smart ... Integrated Photovoltaics Structural electronics involves ... as load-bearing, protective structures, replacing dumb structures such ...
(Date:6/24/2016)... According to a new market ... Needles, Safety Pen Needles), Needle Length (4mm, 5mm, 6mm, ... of Purchase (Retail, Non-Retail) - Trends & Global Forecasts ... market for the forecast period of 2016 to 2021. ... by 2021 from USD 1.65 Billion in 2016, growing ...
(Date:6/23/2016)... , June 23, 2016 Research and ... Global Market - Forecast to 2022" report to their ... treatment method for the patients with kidney failure, it replaces ... fluid from the patient,s blood and thus the treatment helps ... and chloride in balance. Increasing number of ...
Breaking Medicine Technology: