Four research projects conducted by University of Colorado Cancer Center members from the University of Colorado Anschutz Medical Campus and Colorado State University recently each received $50,000 pilot grant funding from the Joint Pilot Program of the CU Cancer Center and CSU Flint Animal Cancer Center.
The 12-month funding promotes inter-campus collaborative research, with the goal of using the research findings and results to support a subsequent multi-year national grant application.
The projects represent a broad and varied spectrum of cancer research, from targeting a novel oncogene implicated in many types of human and canine cancer progression, to identifying biological dependencies in canine osteosarcoma, and studying similarities between human and canine sinonasal carcinoma.
Understanding benefits of companion animals
Linda S. Cook, PhD, associate director for population sciences in the CU Cancer Center, is partnering with Jennifer Currin-McCulloch, PhD, LSW, assistant professor of social work at CSU, and Lori Kogan, PhD, professor of clinical sciences at CSU, to study the benefits breast cancer survivors gain from their companion animals. They also will study the associated stress breast cancer survivors can experience related to their animals’ wellness and decisions about the animal’s future.
“Research pertaining to breast cancer survivors’ support systems has overlooked companion animals,” Cook explains. “Yet pets are typically viewed as family members and can play a key role in survivors’ experiences. With our research, we hope to identify ways that health care providers and community entities can promote this important element of support for the more than 50,000 estimated breast cancer survivors in Colorado.”
Screening every gene in the dog genome
For James Costello, PhD, CU Cancer Center member, and an associate professor of pharmacology in the CU School of Medicine, research conducted in collaboration with Molishree Joshi, PhD, pharmacology instructor in the CU School of Medicine, and Dawn Duval, PhD, associate professor of clinical sciences at CSU, will work to identify essential genetic drivers in a panel of canine osteosarcoma cell lines using whole genome CRISPR-Cas9 screening.
“The goal of the work is to identify genes that when lost kill canine osteosarcoma cells,” Costello explains. “Using a novel platform developed between the two campuses, we can screen every gene in the dog genome simultaneously. We can then match the top hits from this massively parallel gene target screen to drugs that are known to target those genes. This allows us to rapidly identify potentially novel drug treatment strategies in a systematic way.”
The ultimate goal of this research is to identify novel drug treatments “that can be moved into clinical trials for canine osteosarcoma,” Costello says. “If successful, these results would provide strong support for moving the same treatments into humans.”
Studying a novel enzyme inhibitor
Daniel V. LaBarbera, PhD, CU Cancer Center member and director of the CU Skaggs School of Pharmacy and Pharmaceutical Sciences Center for Drug Discovery, and Daniel Gustafson, PhD, Program Co-Leader of the Developmental Therapeutics Program at the CU Cancer Center and a professor of cancer pharmacology at CSU, will focus their research on osteosarcoma as well. Their research will study inhibitors to the Chromodomain Helicase DNA-binding protein 1-Like (CHD1L) under development in the LaBarbera laboratory for the treatment of human cancer.
“What we have done with preliminary data is show that our CHD1L inhibitors are effective against both canine and human osteosarcomas cells,” LaBarbera says. “What this means is that the CHD1L enzyme in dogs is likely structurally very similar to the human enzyme. So, our inhibitors may prove to be effective targeted therapies for both canine and human osteosarcomas.”
Their research will work to determine the dose responses of both canine and human osteosarcoma cell lines to the novel CHD1L inhibitor (CHD1Li). They also will test whether CHD1Li will augment gene expression and sensitize osteosarcoma to cell death when combined with other drugs.
Drawing on shared strengths
CU Cancer Center members Sana Karam, MD, PhD, associate professor of radiation oncology in the CU School of Medicine, and Mary-Keara Boss, DVM, PhD, assistant professor of radiation oncology at CSU, will study possible similarities between human and canine sinonasal carcinoma, drawing from abundant canine research to inform less-abundant human research.
“Sinonasal carcinoma is one of the most aggressive head and neck cancers in human patients,” Karam explains. “And it is rare, making it impossible to run human randomized clinical trials, the gold standard, to test the efficacy of therapeutics. So, we end up basing a lot of therapies by borrowing from other head and neck subsites such as tongue or tonsil, which are different tumor microenvironments, and also from retrospective institutional series where the number of patients studied is very small.”
Because of these borrowed therapies and small sample sizes, outcomes are poor, especially for advanced-stage disease. However, sinonasal carcinoma is highly prevalent in dogs.
“The canine literature is far ahead of the human literature, particularly as it relates to radiation, in understanding the makeup of this cancer and the genetic and immunosuppressive drivers of this disease,” Karam says. “We will draw on the strengths of both institutions to do comparative analysis between dogs and human sinonasal carcinoma to help us better understand the biology of this disease.”