Featured Research

from universities, journals, and other organizations

Genomics used to identify a molecular-based treatment for a viral skin cancer

Date:
May 9, 2012
Source:
University of Pittsburgh Schools of the Health Sciences
Summary:
Four years after they discovered the viral roots of a rare skin cancer, researchers have now identified a molecule activated by this virus that, in animal studies, could be targeted to selectively kill the tumor cells. The treatment will soon be tested in patients.

Four years after they discovered the viral roots of a rare skin cancer, researchers at the University of Pittsburgh Cancer Institute (UPCI) and the School of Medicine have now identified a molecule activated by this virus that, in animal studies, could be targeted to selectively kill the tumor cells. The treatment will soon be tested in patients.

Merkel cell carcinoma (MCC), a skin cancer that is more common among seniors and those with weakened immune systems, could not be readily diagnosed at one time, and it still has a very poor prognosis, said Patrick S. Moore, M.D., M.P.H., and Yuan Chang, M.D., both of the Cancer Virology Program at UPCI and senior authors of a study that appears online May 9 in Science Translational Medicine.

"This research effort shows the speed at which genomics can identify molecular causes for cancer and then point the way toward a rational and targeted treatment," Dr. Moore noted. "Since the inception of the 1971 U.S. National Cancer Act, researchers have strived to discover the underlying problems that trigger tumor development."

In 2008, the team first described the new Merkel cell polyomavirus (MCV) in Merkel cell carcinoma. Within a year, they showed it was responsible for tumor development in most cases of the disease. At least four out of five healthy adults world-wide are infected with MCV, which usually doesn't cause any symptoms.

"The virus remains in the skin cells, and in most cases, no damage is done," Dr. Chang said. "But when mutations occur to this virus, it can cause cancer. Most of the 1,500 new MCC cases per year in the U.S. are caused by MCV infection."

In quick succession, the team devised tests to identify virus-induced MCC, and began unraveling the biochemical pathways that encourage tumor formation. In their latest project, they "knocked out" a key viral protein called T antigen and found that MCV directly elevates a cellular protein called survivin.

Survivin prevents cells from dying and supports cell division, the researchers said. They found that a drug called YM155, which turns off the survivin gene again, was an extremely potent killer of MCC cells in test tubes and was able to suppress the growth of human tumors that had been established in experimental mice. In comparison, 1,360 other drugs -- including most of the common chemotherapy drugs -- were screened and failed to both kill MCC cells and prevent tumor growth at levels commonly achieved in patients. One of these drugs was able to kill tumor cells in culture dishes, but made no impact on the MCC tumors in mice. It remains a promising candidate drug since it may have better activity in people and is readily available.

A multicenter clinical trial of YM155, a still-experimental anti-cancer drug that is made by Deerfield, Ill.-based Astellas, is expected to begin in the next six months to determine its effectiveness in MCC patients. The trial will be led locally by Pitt School of Medicine assistant professor Hussein Tawbi, M.D., Ph.D., and professor John Kirkwood, M.D., who also is co-leader of the UPCI Melanoma Program, through the Eastern Cooperative Oncology Group, a multicenter cooperative group supported by the National Cancer Institute (NCI), part of the National Institutes of Health.

Typically, neither the cause of a cancer nor the target for a cancer drug is initially known, so most treatments have developed over decades through trial-and-error. Most therapies affect both healthy tissues and cancer cells, resulting in side effects that limit the drug dose that can safely be given. This study, in contrast, was a "rational" drug study where the underlying cellular defect caused by the virus was first discovered through genetic studies and then a drug targeting this process was tested.Survivin is needed during fetal development, but not in healthy adult cells, and YM155 was not toxic to the mice.

"Scientists can now quickly come up with answers to complex problems, like cancer, using human genetics," Dr. Moore noted. "In less than five years, we have gone from knowing very little about MCC to knowing its exact cause and are devising new, precisely targeted and less-toxic therapies."

Prior to their work on MCV, the Chang and Moore lab team discovered another virus, a new human herpesvirus, in 1994 that causes Kaposi's sarcoma, the most common cancer among AIDS patients.

Co-authors include Reety Arora, Masahiro Shuda, Ph.D., Anna Guastafierro, Huichen Feng, Ph.D., Tuna Toptan, Ph.D., Yanis Tolstov, Ph.D., Daniel Normolle, Ph.D., Laura L. Vollmer, Andreas Vogt, Ph.D., Alexander Dφmling, Ph.D., and Jeffrey L. Brodsky, Ph.D., all of the University of Pittsburgh.

The research was funded by NCI grants CA78039, CA136363, CA120726 and P30CA047904, and the American Cancer Society. The authors declare that no funding from Astellas or other companies was used for this study.


Story Source:

The above story is based on materials provided by University of Pittsburgh Schools of the Health Sciences. Note: Materials may be edited for content and length.


Journal Reference:

  1. R. Arora, M. Shuda, A. Guastafierro, H. Feng, T. Toptan, Y. Tolstov, D. Normolle, L. L. Vollmer, A. Vogt, A. Domling, J. L. Brodsky, Y. Chang, P. S. Moore. Survivin Is a Therapeutic Target in Merkel Cell Carcinoma. Science Translational Medicine, 2012; 4 (133): 133ra56 DOI: 10.1126/scitranslmed.3003713

Cite This Page:

University of Pittsburgh Schools of the Health Sciences. "Genomics used to identify a molecular-based treatment for a viral skin cancer." ScienceDaily. ScienceDaily, 9 May 2012. <www.sciencedaily.com/releases/2012/05/120509154236.htm>.
University of Pittsburgh Schools of the Health Sciences. (2012, May 9). Genomics used to identify a molecular-based treatment for a viral skin cancer. ScienceDaily. Retrieved October 23, 2014 from www.sciencedaily.com/releases/2012/05/120509154236.htm
University of Pittsburgh Schools of the Health Sciences. "Genomics used to identify a molecular-based treatment for a viral skin cancer." ScienceDaily. www.sciencedaily.com/releases/2012/05/120509154236.htm (accessed October 23, 2014).

Share This



More Health & Medicine News

Thursday, October 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Fears Keep Guinea Hospitals Empty

Ebola Fears Keep Guinea Hospitals Empty

AP (Oct. 23, 2014) — Fears of Ebola are keeping doctors and patients alike away from hospitals in the West African nation of Guinea. (Oct. 23) Video provided by AP
Powered by NewsLook.com
Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) — Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) — Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
More People Diagnosed With TB In 2013, But There's Good News

More People Diagnosed With TB In 2013, But There's Good News

Newsy (Oct. 22, 2014) — The World Health Organizations says TB numbers rose in 2013, but it's partly due to better detection and more survivors. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins