Team to study novel compound that blocks glucose transporter protein crucial to cancer cell growth.
Jefferson researcher Susan Lanza- Jacoby, PhD, has been awarded a two-year grant by the National Institutes of Health (NIH) National Cancer Institute (NCI) to study the use of energy restriction mimetics to slow the progression of pancreatic cancer, reduce the incidence of pancreatic ductal adenocarcinoma and improve the survival rate. Dr. Jacoby formally initiated the project in September with Jonathan Brody, PhD, Director of Surgical Research and Co-director of the Jefferson Pancreas, Biliary and Related Cancer Center, and Jordan Winter, MD, FACS, Associate Professor, Sidney Kimmel Medical College at Thomas Jefferson University.
As Dr. Jacoby explains, cancer cells require a lot of glucose, or energy, to grow. Energy restriction mimetics is the process of limiting glucose to hinder cancer cell growth. In one of her previous studies, Dr. Jacoby found that cutting the caloric intake of mice by 25 percent reduced the number of animals who developed pancreatic cancer. For this new study, the team will test whether and to what extent a new compound, known as CG5, has the same effect. They are collaborating with the Ohio State University medicinal chemist, Dr. Ching-shih Chen, who developed the compound. While Jefferson’s is the first study to focus on CG5 for pancreatic cancer, previous studies have found that the compound inhibits the growth of colorectal and prostate cancer cells in mice. “By inhibiting glucose metabolism, the compound acts, in a sense, like food or calorie restriction,” she says. “More specifically, CG5 inhibits the glucose transporter 1 protein, or GLUT1, which is necessary for glucose to get in the cell and be broken down into energy. The hope is that by inhibiting GLUT1, CG5 will ‘starve’ pancreatic tumors.”
This early-stage study will use transgenic mice in which every cell contains additional foreign DNA. This extra DNA enables researchers to study gene function or regulation and to model human diseases. Researchers will be analyzing whether and how much the compound inhibits carbohydrate metabolism and transport and utilization of glucose.
“We will see if we can inhibit the growth of what we call precursor cancerous lesions – advanced lesions in the pancreas that progress to pancreatic cancer,” Dr. Brody explains. “We’ll also be exploring how the compound affects the RNA binding protein, HuR, which we’ve been studying in our laboratory for a number of years.
“In other studies, we’ve found that inhibiting HuR makes pancreatic cancer cells more sensitive to chemotherapy. We hypothesize that the CG5 compound may also inhibit HuR, thereby yielding better chemotherapy outcomes.”
Dr. Jacoby emphasizes that this is a very early-stage, mouse-model study, and it will take extensive research, including additional animal studies and a toxicity profile, to determine whether or not the CG5 compound can be safely used in humans.
“It’s too soon to translate this for humans,” she notes. “Ultimately, though, the goal is to develop a drug that will alter metabolism to reduce the incidence and progression of pancreatic cancer – without requiring people to slash their caloric intake.”
"Dr. Lanza-Jacoby Secures Two-Year Grant from NIH National Cancer Institute,"
Jefferson Surgical Solutions: Vol. 10
, Article 6.
Available at: https://jdc.jefferson.edu/jss/vol10/iss2/6