Researchers receive NSF grant to explore system theoretic approaches for cancer drug discovery
Two researchers from the Texas A&M Engineering Experiment Station (TEES)-AgriLife Center for Bioinformatics and Genomic Systems Engineering (CBGSE) and the Department of Electrical and Computer Engineering at Texas A&M University have received a grant from the National Science Foundation (NSF) that will allow them to explore the use of system theoretic approaches to carry out cancer drug identification.
Dr. Michael Bittner’s (left) and Dr. Aniruddha Datta’s (right) grant, “Identification of Drug Targets and Their Validation in Cancer Therapy Design,” is a three-year, $400,000 grant. Their project proposes a novel approach to combine pathway information concerning cancer cell life and death along with data on modes of cell response to drugs to develop models that would allow the identification and validation of decisive modulators of cell death.
Bittner has tested some drug combinations in cancer cell lines and mice,” Datta said. “His basis for coming up with these drug combinations is his expert knowledge as a biologist. What we want to do with this grant is to see whether we can use engineering methods to do the actual modeling, and see whether those models suggest the same kind of combinations that he came up with as a biologist.”
Their project builds upon the recent robust induction of cancer cell death that Bittner and his collaborators in the Texas A&M School of Veterinary Medicine were able to experimentally demonstrate using canine cancer cell lines. Bittner worked with Dr. Heather Wilson-Robles, associate professor and Dr. Fred A. and Vola N. Palmer Chair in Comparative Oncology, to successfully test his therapy on canine osteosarcoma, a type of bone cancer in aging dogs. The drugs in this case were chosen based on Bittner’s expert knowledge. The focus of their current project is to develop a systematic approach to identify highly potent modulators.
“We want to see if we can make that knowledge systematic because it would have applications in other cancers and also agricultural genomics,” Datta said. “I’m really excited about being involved in the research proposed in this grant because in this particular case, Bittner has already had experimental success. So now the question is can we reverse engineer that and come up with Bittner’s combination and perhaps more?”
Current cancer drugs targeted at checking cell proliferation have generally had limited success as cancer cells usually apply alternative mechanisms to bypass anti-proliferative drug activities. However, Bittner and Datta hope rapid and robust induction of cancer cell death may provide a more potent weapon against the disease.
“Most people are targeting how to prevent the cancer cell from multiplying, and that has met with limited success,” Datta said. “The wiring is so complicated inside the cancer cell that more often than not, you test a drug that you think will work and the cell figures out a way to bypass the drug. What Bittner is trying to do is kill the cancer cells. If you can rapidly kill all or nearly all of a patient’s cancer cells with a potent drug combination many possibilities arise. A full cure, via the initial cancer cell death, a cure spurred by typical cancer cell killing via the immune system, or the ability to apply the drugs again should the cancer recur, that’s what’s exciting.”
Bittner agrees. “Most cancer patients get three to four months longer survival with what is a considered a successful drug, a very limiting and expensive situation for many cancer patients,” he said, adding that because his goal is aimed at maximum elimination of cancer cells, the chance of reoccurrence is reduced. “Application of jointly developed methods could be used to identify other kinds of drugs which might well have powers that we haven’t figured out as biologists yet.”
With their current grant, the hope is that Robles would continue to support their research with samples and information, but the ultimate goal would be to secure another grant to fuel increased collaboration with the School of Veterinary Medicine and larger animals. “When you do these studies in mice getting them to scale up to humans is much more difficult,” Datta said, adding that dogs are closer to humans, therefore positive results have more impact.
Bittner, a research professor with the TEES-AgriLife CBGSE, joined the center in January 2014. He is also associated with the Translation Genomics Research Institute (TGen) in Phoenix, where he served as co-director of computational biology from 2003-2013. Prior to that, he was with the National Human Genome Research Institute of the National Institutes of Health (NIH) and previously worked for Monsanto and Amoco.
His research interests mainly center around cancer cell dynamics and, with the relocation of his lab to College Station, tremendous opportunities have opened up for cancer drug identification and testing using canine samples.
Datta, the J.W. Runyon, Jr. ’35 Professor II in Electrical and Computer Engineering, joined the department in 1991. He also currently serves as the director of the TEES-AgriLife CBGSE and is responsible for developing research collaborations between the Texas A&M College of Engineering and Texas A&M AgriLife Research.
Datta's research focuses on robust adaptive control, PID control, engineering issues related to cancer genomics and most recently on plant genomics issues motivated by agricultural applications.