The Academy: June 2007

By Prachi Petal-Predd
Published: Thursday, Jul 15, 2010
%u25BA The University of Texas M.D. Anderson Cancer Center, Houston

Assessment Model for Lung Cancer Risk

Researchers at The University of Texas M.D. Anderson Cancer Center in Houston, TX have developed a model that could help clinicians assess which smokers are at higher risk for developing lung cancer. It is the first to use standard clinical and epidemiological data such as smoking habits; exposure to environmental tobacco smoke; family history of cancer; hay fever; and exposure to dust or asbestos.

Smoking is the primary cause of 85% of all lung cancers, less than 20% of lifetime heavy smokers actually develop lung cancer, the study’s lead author Margaret Spitz, MD, professor and chair of the department of epidemiology at M.D. Anderson told Oncology & Biotech News. “It is important to be able to identify high risk subgroups of smokers for intensive smoking cessation and screening interventions,” she said. “More importantly, we could intensively screen this population with modalities that might not be appropriate for the average at-risk population.”

The new model assigns a score that represents a patient’s estimated risk for developing the disease. Clinicians can use the new model to compute a patient’s ordinal risk score and the patient’s absolute chance of developing lung cancer within a year. They can then classify patients into high-, moderate-, or low-risk groups. Currently, the model’s prediction accuracy is about 60%, which is on par with that of the Gail model for breast cancer, according to the researchers. The researchers are in the process of developing a web-based version of their tool, which Dr. Sptiz said will be available for clinicians soon.

Dr. Spitz and colleagues developed and tested the new model by comparing the medical history of 1,851 lung cancer patients with the same data from 2,001 healthy people. The population included current and former smokers as well as people who had never smoked. The researchers divided the cases and controls into two groups. They used one for building the model and the second for testing and validating the model.

The key risk factors in the targeted groups were predictable in some cases. For example, in people who had never smoked, the risk came from exposure to secondhand smoke and family history of cancer. But in current and former smokers, the researchers found that there was a strong impact of a prior history of emphysema as a risk factor.

%u25BA Dana-Farber Cancer Institute and Harvard Medical School, Boston

Diabetes Drug Boosts Efficacy of Platinum Chemotherapy Agents

A widely used diabetes drug and a platinum-based chemotherapy drug have proven to be a potent combination in targeting cancer when administered together to a variety of cancer cell lines and to mice with tumors, according to a study published in the May issue of Cancer Cell. Researchers at the Dana-Farber Cancer Institute in Boston, MA reported in the study that a combination of carboplatin and the diabetes drug Avandia (rosiglitazone maleate) was as much as three times more effective at halting or shrinking mouse tumors than either drug given alone.

The drug combination could improve control of ovarian, lung, and other cancers that are typically treated with platinum-based drugs, to which tumors eventually develop resistance, the researchers said.

Avandia, which enhances the sensitivity of insulin receptors in diabetics, was approved in 1999 for use by patients with type 2 diabetes. The drug works by activating PPAR-gamma, a transcription factor that acts as a master regulator of fat development in the body. Bruce Spiegelman, PhD, professor of cell biology at the Dana-Farber Cancer Institute and Harvard Medical School in Boston, MA, and his colleagues had discovered this function of PPAR-gamma in 1994. They had also found that certain PPAR-gamma-activating compounds halted cancer cell growth and differentiation.

Since previous studies had shown that rosiglitazone alone was ineffective against various cancers, the researchers tried these agents in combination with platinum-based chemotherapy agents. They also tested a similar diabetes drug pioglitazone and an experimental compound by GlaxoSmith¬Kline, combining these drugs with the commonly used chemotherapy agents cisplatin, carboplatin and oxalyplatin.

Dr. Spiegelman and his colleagues found that treating non small-cell lung cancer cell lines with rosiglitazone alone did not have any effect on growth, while carboplatin alone reduced cell growth by 60%. But when used together, the drugs reduced cell growth by 80%. The drug combination reduced ovarian cancer cell growth by 90%, and even reduced the growth of colorectal cancer cells by 70%—colorectal cancer is not usually treated with platinum drugs. Moreover, the drug combination dramatically suppressed tumor growth when administered to mice with human lung and ovarian tumors implanted under their skin.

%u25BA University of Wisconsin-Madison Medical School

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