Pelotonia Grant, Personal Experience Drive Survivor's Gene-Based Breast Cancer Research
Ramesh Ganju, PhD, has spent his career examining deadly diseases at the molecular level.
And now, with funding from a Pelotonia Idea Grant, Ganju is studying triple-negative breast cancer (TNBC) and the role of a specific gene, S100A7, in the formation and metastasis of this somewhat rare and more-deadly type of breast cancer that seems to disproportionally affect African-American women.
Ganju has become even more motivated in recent years. He was diagnosed with stomach cancer three years ago.
“I want to do my best to help develop better treatments for cancer patients,” says Ganju, a member of the Molecular Biology and Cancer Genetics Program at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James). “I know what they go through, and I know how important research is.”
Three hormonal receptors are known to fuel the growth of the majority of breast-cancer cases: estrogen receptors, progesterone receptors and human epidermal growth factor receptor 2 (HER2). These three receptors are not present in TNBC, which is why it is called triple-negative.
“For patients with one of the three receptors, there are therapies available, targeted therapies that can block these receptors,” Ganju says. “With TNBC, because they lack these three receptors, it is more difficult to treat. There are no targeted therapies. We have to treat TNBC with chemotherapy, which isn’t as effective (as the targeted therapies) and has more side effects.”
Breast cancer is the second leading cause of cancer death among women. There will be an estimated 252,000 new cases diagnosed in women in 2017 in the United States and 40,000 deaths, according to the National Cancer Institute (NCI). About 15 percent of all breast cancer diagnoses are TNBC, according to the National Breast Cancer Foundation, which notes that this disease “is more likely to affect younger people, African-Americans, Hispanics and/or those with a BRCA1 gene mutation.”
Ganju says TNBC is more aggressive and metastatic than other forms of breast cancer, and it has a higher mortality rate.. The five-year survival rate for Caucasian women with TNBC is 36 percent, but only 14 percent for African-American women, he says, adding that socio-economic factors could play a factor in this, “but it doesn’t explain such a wide disparity.”
The overall five-year survival rate for all women with breast cancer is 89.7 percent, according to the National Breast Cancer Foundation.
Ganju’s initial research indicates the S100A7 gene is expressed more in women with TNBC and appears to be expressed even more in African-American women with TNBC than in Caucasian women with TNBC. “We have only done a small patient sample so far, and this (Pelotonia Idea Grant) will help us gather more data,” he says. “We want to find out if it is expressed more in African-American women with TNBC than Caucasian women and what role it might be playing in this aggressive behavior.”
Initial research by Ganju has shown that overexpression of the S100A7 gene leads to more inflammation in mammary glands. And inflammation is a cause of cancer. His study revealed changes in macrophages (cells in the body’s immune system) that impact the tumor’s microenvironment and allow the cancer cells to grow more rapidly.
“We are trying to do two things in this study: establish the connection between S100A7 and TNBC, and see what happens when you do,” Ganju says.
Proving the connection could lead to improved treatment options. “Researchers are already working on neutralizing antibodies that can block the function of S100A7 and inhibit the growth of tumors,” Ganju says. “This would be targeted therapy for TNBC.”
A passion for science and unraveling the mysteries of the body have driven Ganju throughout his career. He came to the OSUCCC – James in 2007. Over the years, he has dived deep into the body’s immune system and “how immune cells are regulated.”
Fortunately, his stomach cancer was diagnosed very early. “Stomach cancer is very rare in Americans, and the survival rate is low,” Ganju says. “My tumor was very small, only one centimeter, but very aggressive, and it would have metastasized and spread in one month.” He underwent surgery to remove his stomach, followed by chemotherapy and radiation treatments at the OSUCCC – James.
“I always try to stay positive, and I never let it affect my work; I worked right through all my treatments,” he says. “It has changed my outlook. It’s made me more determined, and it’s also taught me to enjoy whatever time you have left and not to get bothered by the little things.”