Like most cancers, breast cancer is most treatable when caught early. Through a recent California Breast Cancer Research Program grant, City of Hope’s Daniel Tamae is working on a method for spotting the disease when it is just beginning to form, potentially giving patients better odds for cure.

While national data show a downturn in incidence of new breast cancer cases in recent years, the disease remains the second most frequently diagnosed form of cancer in women — and the second most deadly — making early detection paramount.

Graduate student Daniel Tamae is developing a method to detect cancer in its earliest stage. (Photo by Darrin S. Joy)

The biomarker stems from a well-known feature of cancer cells called the “Warburg effect,” so named after its discoverer, Nobel Laureate Otto Warburg. The Warburg effect notes that many different types of cancers get their energy by using high levels of the sugar glucose.

The high levels of glucose in cancer cells result in by-products that may react with proteins, fats, DNA and other cellular molecules to form what are known as advanced glycation end-products, or AGEs. This process is called glycation.

Working from a tip by Samuel Rahbar, M.D., Ph.D., professor in the Division of Diabetes, Endocrinology & Metabolism and a noted expert on AGEs, Tamae turned his sights on certain AGEs as possible cancer markers. Specifically, these AGEs come from the reaction of glucose by-products with DNA.

“The AGE we’re interested in is called CEdG,” said Tamae. “It’s one of the most prevalent forms of DNA glycation.” CEdG is likely to play a role in cancer development and so could be a good biomarker for detecting the disease early on, he added.

To measure CEdG levels, Tamae turned to Gerald Wuenschell, Ph.D., senior research fellow in the Department of Molecular Biology, and Timothy Synold, Pharm.D., co-director of City of Hope’s Analytical Pharmacology Core Facility. Wuenschell and Synold collaborated to create a sensitive, accurate and reliable way to measure CEdG in human tissue and urine samples.

Armed with a way to measure CEdG levels, Tamae will compare levels of the AGE in urine and tissue samples from both healthy volunteers and breast cancer patients. Arti Hurria, M.D., director of the Cancer and Aging Research Program, collects tissue samples for later analysis by Tamae.

If results clearly link CEdG levels and cancer, the CEdG biomarker could be used not only for early screening and detection of breast cancer, but also to track a patient’s treatment progress, according to Termini. “That may be where the most immediate value lies,” Termini said.

Today, physicians often use positron emission tomography, or PET, to check a tumor’s response to treatment. PET is expensive and requires a patient to lie still in a scanner for a relatively long time period. “Measuring CEdG levels, particularly in urine samples, would be much more convenient for the patient and probably less expensive once the technique is established,” explained Termini.

Scientists are still unsure what roles DNA glycation and CEdG play in cancer development, so Tamae also is studying CEdG’s influence in mutating DNA, as well as how the body limits CEdG’s effect.

“We’re charting new territory here,” said Tamae. “It’s exciting to see some interesting results, particularly when they could really benefit patients down the line.”

This research project also recently netted Tamae a Pfizer Young Investigator’s award from the American Chemical Society’s Division of Chemical Toxicology in August.

Established in 1993, the California Breast Cancer Prevention Program is the largest state-funded research effort in the nation. The program’s dissertation awards were introduced in 2003 and fund up to a two-year project for masters- or doctoral-level graduate students who wish to pursue breast cancer-related research.