Researchers report discoveries in cancer progression and rare skin and pancreatic cancers


  • Carrie Printz

Scientists from around the world gathered in San Francisco, California, for the Second American Association for Cancer Research MACR) International Conference on Frontiers in Basic Cancer Research, held September 14 to 18, 2011. Among featured studies were:

Progression Studies May Lead to Targeted Therapies

Researchers are working on understanding how genes interact to trigger cancer progression, anticipating that their findings may lead to new targeted therapies for breast cancer.

The investigators found that a diuretic used to treat hypertension and edema also stops breast cancer cells from progressing and, in culture, appeared to be as effective as several cancer drugs on the market. Bin Zhang, PhD, principal scientist and group leader at Sage Bionetworks in Seattle, Washington, says the treatment may eventually be tested in human clinical trials but still has a long way to go. His group predicted and validated the drug's effectiveness in preferentially killing cancer cells by inhibiting cell cycle pathways responsible for uncontrolled cell proliferation.

The researchers analyzed multiple, large-scale cancer genomic data sets to find novel pathways and driver genes that help breast cancer progress. They then tested them against various compounds anti drugs to determine how they would react. The research indicated that many genes work as groups that correspond to different pathways. The researchers concluded that future targeted therapies will be more effective they target more than 1 pathway and that combination therapy may work better against different pathways.

The researchers developed complex and advanced algorithms to reconstruct multiscale gene regulatory networks that reveal global patterns of gene interactions in cancer and also detail regulatory maps, says Dr. Zhang. He adds that the networks will serve as blueprints for understanding cancer progression and developing novel therapeutics.

Virus Induces Rare Skin Cancer

How the virus that causes most forms of Merkel cell carcinoma operates is a research focus for scientists at the University of Pittsburgh Cancer Institute in Pittsburgh, Pennsylvania. The group hopes that better understanding of this virus and its effect on this rare and aggressive skin cancer may lead to effective chemotherapeutic targets. Merkel cell carcinoma incidence has increased 4-fold during the last 20 years, particularly in immunosuppressed populations, says Patrick Moore, MD, MPH, a member of the research team.

Not only is the cancer difficult to treat, but most clinical trials of drugs targeting it have been disappointing, says Dr. Moore. In 2008, he and colleagues discovered Merkel cell polyomavirus (MCV), which is believed to cause 80% of Merkel cell carcinomas. Their laboratory also discovered the herpes virus that causes Kaposi's sarcoma, which is common in patients with acquired immune deficiency syndrome.

MCV is a natural component of human skin and is generally harmless; however, among people who are immunodeficient, it undergoes specific mutations that can generate Merkel cell carcinoma. The researchers have discovered a variety of unique characteristics of the virus, including:

  • MCV small T antigen protein is a new oncogene that can contribute to abnormal cell growth in both rodent and human cells.

  • MCV does not act the same as other polyomaviruses that have served as classic models of cancer. Others depend on viral interaction with the enzyme protein phosphatase 2A (PP2A and heat shock proteins. MCV interacts with, but does not depend on, these enzymes and proteins. It can still cause abnormal cell growth, even after abolishing PP2A and heat shock protein binding sites.

The team hopes to develop treatments that will target the pathways affected by MCV. They have tested more than 1350 drugs to identify ways to better target this cancer.

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Virus May Help Image and Treat Prostate Cancer

The vaccine virus construct GLV-1h53,which is engineered to encode for the human sodium iodide symporter gene (hNIS), may provide effective virotherapy for cancer as well as a means of monitoring therapeutic response through imaging methods such as positron emission tomography. In addition, it can be used for targeted radiotherapy, according to researchers at Memorial Sloan-Kettering Cancer Center in NewYork, NewYork, and Genelux Corporation.

In their study, more than 50 mice were treated and imaged with GLV-1h53 to gain insight into tumor therapeutic response, according to Dana Haddad, MD, PhD, who previously was with Memorial Sloan-Kettering Cancer Center and is now at the Mayo Clinic in Phoenix/Scottsdale, Mizona. The virus construct was also combined with radioiodine for targeted radiotherapy of pancreatic tumors.

Dr. Haddad says she and colleagues initially were discouraged when the positron emission tomography signal pancreatic tumors began to disappear after 2 weeks of treatment with the virus, but they soon learned that its disappearance likely was the result of tumor killing activity and necrosis. They also discovered that by using lower doses the virus along with radiotherapy, they could more effectively kill the tumor while at the same time minimizing toxicity and side effects associated with both therapies.