Scientists at the Mayo Clinic campus in Florida have found that the lung cancer oncogene PKCiota is necessary for the proliferation of lung cancer stem cells. These stem cells are rare and powerful master cells that manufacture the other cells that make up lung tumors and are resistant to chemotherapy treatment.
Their study, published in the Oct. 1 issue of Cancer Research, also shows that an agent, aurothiomalate, being tested at Mayo Clinic in a phase I clinical trial substantially inhibits growth of these cancer stem cells.
"Our data indicate that PKCiota is required for the earliest steps in the development of lung cancer, which is the expansion of tumor-initiating cells or cancer stem cells," says the study's senior author, Alan Fields, Ph.D., professor of pharmacology in the College of Medicine, Mayo Clinic, and chair of the Department of Cancer Biology at Mayo Clinic's campus in Florida.
"Lung cancer stem cells appear to be the major drivers in many common lung cancers, and in order for a therapeutic treatment to be effective, it has to disrupt these cancer stem cells," he says. "We show that aurothiomalate, the agent now being tested in lung cancer patients, can, in fact, target these cells."
Aurothiomalate was once used to treat rheumatoid arthritis, but the Mayo Clinic researchers discovered by screening thousands of Food and Drug Administration-approved drugs that it also can target PKCiota. The agent is being tested in patients at Mayo Clinic's sites in Minnesota and Arizona and, based on this phase I trial, a phase II human clinical trial is planned to combine aurothiomalate with agents targeted at other molecules involved in cancer growth.
Dr. Fields and his colleagues were the first to discover that PKCiota is a human oncogene - an abnormal gene that cancer cells use to grow and/or survive. They found that PKCiota is genetically altered and over-expressed in a majority of lung cancers and that over-expression of the PKCiota gene in tumors predicts poor patient survival.
"We had previously shown that PKCiota is required to maintain tumor growth, but what this study sought to determine is whether PKCiota is involved in the initial steps of lung cancer development," Dr. Fields says.