INDIANAPOLIS (WISH) - From a lab at IU Simon Cancer Center , two researchers have started a journey that may be groundbreaking in the fight against pancreatic cancer.
Mark Kelley, Ph.D. , Associate Director of Basic Science Research at IU Simon Cancer Center and professor of pediatrics, and Melissa Fishel, Ph.D. , assistant research professor of pediatrics, were awarded a five year grant worth $3.2 million from the National Cancer Institute . The two researchers have assembled a team of nationally recognized specialists to study a protein that could regulate the development and resistance of pancreatic cancer tumors.
"What we've learned over the last few years is that although we're decent at killing tumor cells, it [pancreatic tumors] has this complex network of other types of cells that form a ball, or sphere, around the tumor," says Fishel.
The sphere is known as a microenvironment, made up of blood vessels and other cells that are helping the tumor survive. One of the hallmarks of this disease is the fibrosis that accompanies the cancer. This fibrosis – the formation of excess fibrous connective tissue – engulfs the tumor like a sphere, preventing chemotherapy from penetrating and killing the tumor. Drs. Kelley and Fishel say the fibrosis is partly why about 95 percent of people with pancreatic cancer die from it.
"So we've learned that we can't just treat the tumor, we have to treat the whole system, or the microenvironment, and our protein regulates some of the genes that are important in causing this resistance that can help to penetrate the fibrosis," says Fishel.
In their laboratory research, Drs. Kelley and Fishel plan to block a protein, redox factor 1 (Ref-1), which is crucial to regulating pancreatic tumor growth and metastasis. The team will use a protein inhibitor that Dr. Kelley and colleagues developed that has shown promise in the lab in blocking Ref-1.
The team has worked for nearly seven years publishing research to prove their protein inhibitor could kill pancreatic cancer in mice. The grant will allow them to test the protein inhibitor on human samples from current pancreatic cancer patients of IU Simon Cancer Center.
"We've found our target protein is interacting with a number of other proteins called transcription factors and this is helping them to do their job [of developing cancer] better," says Kelley. "We're hoping that if we can inhibit the function of Ref-1, we can blunt the tumor's ability to live or grow."
Kelley explains the team's goal is to have molecules developed that attack the target protein (Ref-1) that will then be used in clinical trial.
There are two types of pancreatic cancer: exocrine tumors and endocrine tumors. Exocrine tumors are the majority of pancreatic cancers, and the most common form is called adenocarcinoma , which is the type Stephanie Gahimer, 37, from Indianapolis was diagnosed with in December 2011.
"There was a part of me that knew something wasn't right," says Gahimer. "I went to the doctor to have lab work done and I got a call from the doctor's office the very next morning asking me to come back in for another test."
Gahimer says the functions of her liver and pancreas "were off," prompting doctors to redo the lab work, at which point they sent her straight to the hospital where doctors discovered her pancreatic cancer. Soon after, she had surgery to remove the tumor and was declared cancer-free. However, her surgery was followed by 6 months of chemotherapy, 5 ½ weeks of radiation, and then 3 more months of chemotherapy.
"I didn't want [doctors] to tell my parents 'your child has a 6 percent survival rate.' I was actually very lucky and was told all along that I wouldn't be a statistic," says Gahimer.
Pancreatic cancer is the fourth-leading cause of death from cancer in the United States, after lung, colon and breast cancer. The lifetime risk of developing it is about 1 in 71. The National Cancer Institute estimates 45,220 Americans will be diagnosed with cancer of the pancreas in 2013, 38,460 will die, and most of them will be over 65 years old.
Drs. Kelley and Fishel will collaborate with other IU Simon Cancer Center researchers: internationally recognized cancer researcher Murray Korc , M.D., tumor microenvironment and metastatic expert Theresa Guise , M.D., and hypoxia expert Mircea Ivan , M.D., Ph.D.
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