Researchers Seek New Methods To Find, Fight Cancer
By LaTina Emerson
For generations, cancer has been one of the most feared diseases.
Many patients and even doctors wouldn’t use the word “cancer,” and obituary writers often referred to people dying after a “long illness” so they could avoid the term.
Though diagnosis and treatment has improved dramatically, and the stigma has eased, cancer is still a leading cause of death. In the U.S. this year, the American Cancer Society estimates there will be nearly 1.7 million new cancer cases diagnosed and 585,720 deaths.
Scientists at Georgia State University are working on research projects to better understand cancer, a group of diseases characterized by uncontrolled growth and spread of abnormal cells. They are working to develop more effective diagnosis and treatments, and hoping to ultimately eliminate cancer.
Here’s a look at some of that research:
Zhi-Ren Liu, professor of biology, and Jenny Yang, professor of biochemistry and biophysics, are developing a new injectable protein (ProCA) for use during MRI scans that can circulate in the body up to several hours, to provide brighter, more detailed images on the molecular level.
This new protein, referred to as a probe, is designed to aid in diagnosis and treatment, allowing doctors to see whether a patient has certain molecules that can indicate cancer and the progression of cancer. The researchers are studying liver cancer and HER2–positive breast cancer in pre-clinical studies.
Liver cancer patients have a better chance of survival if cancer is detected earlier. In HER2-positive breast cancer, in which the cancer cells produce the HER2 protein on cell surfaces, the researchers will determine if patients should receive the drug Herceptin based on images made using ProCA.
The research is funded by the National Institutes of Health.
Chemistry Professor Binghe Wang has developed a fluorescent molecule that can be delivered to cancer cells to illuminate them. The molecule could aid diagnosis and also guide surgeons by helping make sure they don’t fail to remove cancerous tissue.
“It’s not always easy when you do cancer surgery to clearly define where the boundaries are,” Wang said. “One of the characteristics of cancer is that in a solid tumor, the boundaries are not clear. Fluorescent molecules that mark cancer cells will be very useful.”
Wang is also working on a type of anti-cancer drug that regulates the levels of p53, a protein that induces cell death.
In some forms of cancer, the cancer cells suppress the level of p53, protecting the cancer cells. Wang has developed a group of compounds that removes cancer’s ability to suppress this protein.
In a study with mice with acute lymphocytic leukemia, all of those who received Wang’s compounds lived and maintained a healthy weight. In the group that did not receive the treatment, all of the mice lost weight and died within 50 days.
“We saw a cure in mice with acute lymphocytic leukemia with no relapse within a year (the duration of the study), which is remarkable,” Wang said. “What’s also very, very important is that we saw no toxicity with the compound.”
He has seen positive results in cell culture studies on tumors and believes the treatment will work on other forms of cancer.
Wang, who collaborated with Muxiang Zhou at Emory University, is looking for a pharmaceutical company interested in licensing the product and conducting trials in the hopes of getting a cancer drug on the market.
He is also studying a protein complex that can inhibit tumor growth. Tumors need to develop more blood vessels to grow. However, this blood vessel formation is irregular and some parts of the tumor will lack oxygen, a condition called hypoxia.
That lack of oxygen can trigger a chain of events that can lead to faster tumor growth, drug resistance and metastasis. Wang has developed a class of molecules that blocks the process.
In mice treated with his molecular compound, tumors were one-sixth the size of those in mice who did not receive the compound. The experiment on mice involved several types of cancer, lung cancer, pancreatic cancer, brain cancer and metastatic melanoma, or skin cancer that has spread throughout the body.
“What’s also very important is that our compound shows no toxicity because it targets a specific pathway, and the pathway is not supposed to be active in normal cells. It’s only supposed to be active in solid tumors,” said Wang, who collaborated with Erwin Van Meir at Emory University.
In other research, Liu and Yang have designed a protein called proagio, which inhibits blood vessel growth and could shrink and eliminate tumors by destroying their blood vessels. They designed proagio by modifying a human protein.
Proagio has been successful in animal models, and the researchers plan to move to clinical trials in about a year. The protein could create a new platform for treatment of cancers, diseases involving other types of tumors and even age-related macular degeneration. Liu said the product is more effective than others on the market, none of which can eliminate new vessel growth.
Enlisting The Immune System
Charlie Garnett Benson and Susanna Fletcher Greer, researchers in the Biology Department, are studying cancer immunotherapy. The approach, which uses the body’s own immune system to fight cancer, was cited as the top scientific breakthrough of 2013 by Science magazine.
The researchers, assisted by Ph.D. students Anita Kumari and Ercan Cacan, are looking at how radiation can stimulate immune cells, such as T-cells, to attack and kill cancer cells. They are studying breast and colorectal cancer.
T-cells need two signals before they will attack other cells, preventing them from freely destroying healthy cells, which could result in autoimmune disease, Benson said.
“We’re finding that therapies like radiation seem to increase the expression of this second signal on tumor cells,” Benson said. “The T-cell sees that and not only does it want to kill that tumor cell, but once it receives the signal, it can further promote the survival and activation of those T-cells.”
Previously, Benson’s lab found radiation causes genes that stimulate T-cells to have more receptors on cell surfaces. The researchers wanted to study how radiation is changing the behavior of genes in tumor cells and began collaborating with Greer’s lab.
Greer’s lab focuses on epigenetics, the study of how gene expression changes by modifying key proteins without altering DNA.
“Epigenetic changes are now recognized to be as important to cancer formation as are gene mutations,” Greer said. “Because epigenetic states can be altered, epigenetic therapies hold promise as anti-cancer therapies.”
In their study with colorectal tumor cells, the researchers found low-dose radiation increased the survival and activation of T-cells. Also, increased expression of the second signal needed for T-cells to attack cancer cells was controlled by an epigenetic mechanism, Benson said.
The findings could lead to therapies that are more targeted on cancer cells and less toxic for patients, such as combining low dose radiation and immunotherapy.
Exploring Racial Disparities
Ritu Aneja, associate professor of biology, has found a way to identify aggressive forms of breast cancer in African-American women. Her work could help doctors customize treatment for these women.
“Breast cancers have very different outcomes in women from different races,” Aneja said. “In African-Americans, it is characterized by earlier onset, higher aggressiveness, extensive metastases and increased mortality. This is due to fundamental differences in the tumor biology between African-Americans and European Americans.”
Aneja studied a protein called HSET, which is abnormally high in triple-negative breast cancer, a vicious kind of breast cancer most common in African-American women.
She and her colleagues analyzed breast tumor tissue samples from African-American women and non-Hispanic white women. They found samples from African-American women were three times as likely to show high levels of HSET. The researchers were also able to link elevated HSET levels to worse medical outcomes for African-American women, but not white women.
HSET levels appear to be a better predictor of cancer outcomes than other routinely used breast cancer predictors, Aneja said.
She is also studying racial disparities in response to chemotherapy. African-American women are more resistant to conventional chemotherapy than Caucasian women, Aneja said.
She is trying to determine if there is a sequence of genes that will indicate whether an African-American woman will respond to chemotherapy
Aneja hopes her research will result in a test to determine if a particular patient’s cancer will respond to chemotherapy.
Portraits by staff photographer Steve Thackston. Video courtesy of Dr. Ritu Aneja.