Ovarian and pancreatic cancers are among the most deadly, not because they are impossible to cure, but because they are difficult to find. There are no screening tests that can reliably detect their presence in early stages, and most diagnoses are made after the disease already has spread to lymph nodes and vital organs.
But UGA cancer researchers Karen Abbott and Michael Pierce are exploring new methods of detecting these silent killers using the most advanced technologies available. They recently received two, five-year grants from the National Institutes of Health totaling more than $4.1 million to support their projects. Their work promises to help find the cancers early, when doctors have the best chance to help their patients fight the disease.
“Almost every cancer can be successfully treated if it is diagnosed early enough,” said Pierce, a Distinguished Research Professor in the Franklin College of Arts and Sciences and director of the UGA Cancer Center. “If we and others can identify something that helps us find the cancer very early, we will save lives.”
Both researchers are searching for ways to detect specific kinds of glycans—tiny sugar molecules found on the outside of proteins—that sometimes appear in blood and tissue during the earliest stages of cancer formation. If Abbott and Pierce can isolate these glycomarkers and detect them in blood, they may develop new, noninvasive tests that physicians could use to screen for cancer as part of a regular checkup.
Working at UGA’s Complex Carbohydrate Research Center, a state-of-the-art facility dedicated to medical glycobiology and carbohydrate research, Abbott and Pierce will identify new cancer-related glycans and further define the role of those they already have discovered related to pancreatic, ovarian and breast cancers.
Abbott’s project focuses particularly on the early detection of epithelial ovarian cancer, one of the most common forms of the disease that frequently eludes early detection.
“The problem for finding a marker for cancers like that is that they are all so different,” said Abbott, an assistant research scientist and director of the Post-Translational Modification Program at the UGA Cancer Center.
The only available blood test for ovarian cancer searches for elevated levels of a protein called CA-125, but this test, as well as protein-based diagnostics for other cancers, are notoriously unreliable because proteins tend to undergo significant changes as the cancer develops and grows. Glycans, on the other hand, remain relatively stable.
“What we’re finding is that glycan changes happen early as the cells transition and become cancerous, and this is something that the cell holds on to,” Abbott said.
Pierce’s lab is developing new ways to detect glycomarkers associated with pancreatic adenocarcinoma and invasive ductal carcinoma, the two most common forms of pancreatic and breast cancer, respectively. His lab identified and characterized these targets under a previous NIH grant, but he now hopes to refine them into accurate, repeatable tests.
“In the big world of biomarkers, you’re looking for two things: sensitivity and specificity,” he said. “You want a test that will find all the cancers, but you don’t want to misdiagnose people who don’t have cancer.”
As part of this new grant, Pierce and his colleagues also are expanding their search for more disease-specific glycomarkers by studying two types of cells associated with the early development of pancreatic cancer.
One cell type is called a tumor-initiating cell, because it is believed to be involved in the first stages of cancer development. The other cells are called stellate cells, which surround tumors as they grow. Pierce hypothesizes that these two cell types will secrete cancer-specific glycans into the bloodstream that may be discovered using a simple test.
Ultimately, both Pierce and Abbott hope the glycans they identify and study not only will serve as reliable diagnostics for extraordinarily deadly cancers but also pave the way for future research and collaborative projects exploring these important and understudied molecules.
“We’re at the point now where we have some very strong markers,” Pierce said. “They have worked on 75 or 100 samples. Now we need to do 1,000.”