Researchers use genomics to identify a molecular-based treatment for a viral skin cancer
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 today 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 drugsincluding most of the common chemotherapy drugswere 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."
Dr. Moore also is a Distinguished Professor and American Cancer Society Professor, Department of Microbiology and Molecular Genetics. Dr. Chang also is a Distinguished Professor and American Cancer Society Professor, Department of Pathology. Last week, they were elected to membership in the prestigious National Academy of Sciences. 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.
Journal reference: Science Translational Medicine
- Cancer researchers find key oncoprotein in Merkel cell carcinoma Aug 15, 2011 | not rated yet | 0
- Inner workings of virus responsible for rare skin cancer Sep 15, 2011 | not rated yet | 0
- Newly discovered virus linked to deadly skin cancer Jan 17, 2008 | not rated yet | 0
- Research indicates new virus is culprit, not bystander, in deadly skin cancer Sep 22, 2008 | not rated yet | 0
- How immune cells destroy cancer cells: Researchers elucidate mechanism Jan 17, 2012 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
In recent years, microRNAs (miRNAs) and other non-coding RNAs are small molecules that help control the expression of specific proteins. In recent years they have emerged as disease biomarkers. miRNA profiles have been used ...
Cancer 12 hours ago | not rated yet | 0
Cancer cells spread and grow by avoiding detection and destruction by the immune system. Stimulation of the immune system can help to eliminate cancer cells; however, there are many factors that cause the immune system to ...
Cancer 12 hours ago | not rated yet | 0
Researchers from London's Kingston University have begun a two-year study which could help prolong the lives of people with colorectal tumours.
Cancer 16 hours ago | 5 / 5 (1) | 0
Transformative research from Western University has identified new hormones in the body which may suppress breast cancer and stimulate the regression of breast tumors.
Cancer 16 hours ago | 5 / 5 (1) | 0
(Medical Xpress)—Curtin University researchers have found evidence that targeting specific cells in the body can reverse the effects of cancer on the immune system.
Cancer 17 hours ago | 5 / 5 (3) | 0
(Medical Xpress)—A new study by researchers in the US has shown that an ancient virus can be modified to help in the fight against the simian immunodeficiency virus SIV, which is the equivalent in monkeys ...
16 hours ago | 5 / 5 (3) | 0 |
Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...
10 hours ago | 3 / 5 (2) | 0 |
Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.
13 hours ago | 3.7 / 5 (3) | 0 |
Biological processes are generally based on events at the molecular and cellular level. To understand what happens in the course of infections, diseases or normal bodily functions, scientists would need to ...
13 hours ago | 5 / 5 (4) | 0 |
How can healthy people who hear voices help schizophrenics? Finding the answer for this is at the centre of research conducted at the University of Bergen.
16 hours ago | 4 / 5 (2) | 2
(Medical Xpress)—The way Alzheimer's disease is portrayed by advocacy groups and the media is having undue influence on the euthanasia debate, according to a Deakin University nursing ethics professor.
17 hours ago | not rated yet | 2