BioSpace.com

Biotech and Pharmaceutical
News & Jobs
Search the Site
 
   
Biotechnology and Pharmaceutical Channel Medical Device and Diagnostics Channel Clinical Research Channel BioSpace Collaborative    Job Seekers:  Register | Login          Employers:  Register | Login  

NEWSLETTERS
Free Newsletters
Archive
My Subscriptions

NEWS
News by Subject
News by Disease
News by Date
PLoS
Search News
Post Your News
JoVE

CAREER NETWORK
Job Seeker Login
Most Recent Jobs
Browse Biotech Jobs
Search Jobs
Post Resume
Career Fairs
Career Resources
For Employers

HOTBEDS
Regional News
US & Canada
  Biotech Bay
  Biotech Beach
  Genetown
  Pharm Country
  BioCapital
  BioMidwest
  Bio NC
  BioForest
  Southern Pharm
  BioCanada East
  US Device
Europe
Asia

DIVERSITY

INVESTOR
Market Summary
News
IPOs

PROFILES
Company Profiles

START UPS
Companies
Events

INTELLIGENCE
Research Store

INDUSTRY EVENTS
Biotech Events
Post an Event
RESOURCES
Real Estate
Business Opportunities

 News | News By Subject | News by Disease News By Date | Search News
eNewsletter Signup
Miles
Km80.5

   

Karmanos Cancer Institute Researchers Identify Novel Pathway in Lung Cancer to Make Chemotherapy More Effective


4/6/2011 7:10:51 AM

Abstract # 5537

ORLANDO, Fla., April 6, 2011 /PRNewswire-USNewswire/ -- Scientists at the Barbara Ann Karmanos Cancer Institute in Detroit today presented a study at the American Association for Cancer Research's 102nd Annual Meeting 2011 that identifies a key enzyme in non-small cell lung cancers that could potentially make standard chemotherapy more effective against this highly deadly disease.

(Logo: http://photos.prnewswire.com/prnh/20071106/KARMANOSLOGO)

The title of the poster presentation is, "Ubiquitination of RRM1 by Ring1B (RNF2) promotes its degradation and nuclear export." The presenter is Yingtao Zhang, M.D., Ph.D., research scientist with Karmanos and Wayne State University School of Medicine (WSU SOM).

Her fellow co-authors are Xin Li, M.D., research associate in the Department of Oncology at Karmanos and WSU SOM; Zhengming Chen, Ph.D., assistant professor in the Department of Oncology at Karmanos and WSU SOM; Scott N. Freeman, Ph.D., a former post-doctoral fellow at H. Lee Moffitt Cancer Center now with the Federal Drug Administration; Jun Zhou, M.D., a research scientist formerly with Moffitt Cancer Center; and Gerold Bepler, M.D., Ph.D., Karmanos president and CEO and interim chair of the Department of Oncology at WSU SOM. The research also will be published in the 2011 Proceedings of the American Association for Cancer Research.

The study explored the role of RRM1 (ribonucleotide reductase M1), a key enzyme involved in tumor suppression and one that plays an essential role in the development of lung cancer. It has a dual nature in that while it suppresses tumors, overexpression of RRMI is strongly associated with gemcitabine resistance in various cancers, making chemotherapy less effective.

"The purpose of our research is to investigate the mechanisms that control RRM1 expression and subcellular localization, which are extremely important to understanding RRM1 functions and potentially therapeutic applications," said Dr. Zhang. "RRM1 is crucial for DNA damage repair and effectiveness of the chemotherapy agent gemcitabine. Examining the ubiquitination pathway a pathway through which cellular proteins (i.e. RRM1) are degraded may therefore have therapeutic value.

"This is a totally new research study that hasn't been done anywhere else."

Gemcitabine, described by researchers as a "blockbuster" drug, is used in the treatment of non-small cell lung cancer, along with various other carcinomas including pancreatic, bladder and breast cancer. It is also being investigated for use in esophageal cancer and is used experimentally in lymphomas and various other tumor types.

Researchers have identified a ubiquitin E3 ligase, Ring1B, a protein associated with RRM1. It is one of the most important E3 ligases in the ubiquitination pathway, which plays an essential role in directing the fate and function of many cellular proteins, such as histone H2A, a protein associated with DNA. They also found the protein level of RRM1 is regulated by a proteasome-mediated degradation pathway (i.e. ubiquitination pathway). They discovered that Ring1B is involved in the ubiquitination of RRM1 which leads to RRM1 degradation and translocation from a cell's nucleus to cytoplasm, located outside the nucleus.

The team is continuing its work in understanding whether Ring1B breaks down RRM1 completely so that cancer cells can be destroyed by gemcitabine. Dr. Zhang, however, noted that the complete inhibition of RRM1 and its expression induces cancer cell death.

"It is demonstrated that reduction of RRM1 level can reverse resistance and sensitizes tumor cells to gemcitabine, implicating that targeting the ubiquitination pathway may potentially be effective in treatment of gemcitabine-resistant lung cancer," she said.

Researchers have been studying the ubiquitination of RRM1 for more than two years, headed by Dr. Bepler, who joined the Karmanos Cancer Institute as president and CEO in February 2010. Dr. Bepler said that better therapies must be developed so that non-small cell lung cancer patients derive better outcomes.

"Non-Small Cell Lung Cancer is very difficult to treat," he said. "The usual response rates for patients are about 25 percent, so approximately three-quarters of those patients have very little if any benefit from certain treatments. Knowing up-front which treatment will and will not work allows us to use a targeted therapy that provides the most benefit to the patient for their specific cancer."

Located in mid-town Detroit, Michigan, the Barbara Ann Karmanos Cancer Institute is one of 40 National Cancer Institute-designated comprehensive cancer centers in the United States. Caring for nearly 6,000 new patients annually on a budget of $216 million, conducting more than 700 cancer-specific scientific investigation programs and clinical trials, Karmanos is among the nation's best cancer centers. Through the commitment of 1,000 staff, including nearly 300 physicians and researchers on faculty at the Wayne State University School of Medicine, and supported by thousands of volunteer and financial donors, Karmanos strives to prevent, detect and eradicate all forms of cancer. Its long-term partnership with the WSU School of Medicine enhances the collaboration of critical research and academics related to cancer care. Karmanos is southeastern Michigan's most preferred hospital for cancer care according to annual surveys conducted by the National Research Corporation. Gerold Bepler, M.D., Ph.D., is the Institute's president and chief executive officer. For more information call 1-800-KARMANOS or go to www.karmanos.org.

SOURCE Barbara Ann Karmanos Cancer Institute



Read at BioSpace.com

   

ADD TO DEL.ICIO.US    ADD TO DIGG    ADD TO FURL    ADD TO STUMBLEUPON    ADD TO TECHNORATI FAVORITES