The goal of the Cancer Biology Program, led by Program Director Nathan A. Ellis, PhD, is to identify etiologic mechanisms underlying cancer initiation and progression. As the main basic-science-of-cancer platform for the University of Arizona Cancer Center, the Cancer Biology Program advances fundamental knowledge of the complex biological networks that are deranged in cancer and of interactions between these complex networks and the environment that promote cancer initiation and progression. The research done in the Cancer Biology Program has one primary focus: to discover and understand how cancer works at the most fundamental levels in order to devise approaches to cure and prevent it.
Understanding the biological mechanisms that govern normal cell and cancer cell processes allows our researchers to search for new tests for early detection of cancer, for better diagnostic methods using biological markers, and for more effective and less toxic treatment and prevention strategies. The Cancer Biology Program is organized into three major themes based on the different pathologic features of cancer, including (i) Genomic Instability and the Epigenetic Control of Gene Expression, (ii) Signaling Networks in Carcinogenesis and Tumor Progression, and (iii) Invasion and Metastasis. Our researchers further approach cancer discovery through disease-oriented teams (DOTs)—such as the breast cancer, colorectal cancer, and prostate cancer DOTs—in order to understand the origins of cancer at different sites in the body and the ways in which cancer spreads from its primary site to other places in the body.
Cancer Biology Program Members actively translate their laboratory discoveries into new strategies for cancer prevention and treatment. For example, investigators are using cutting-edge technologies to characterize genetic signatures in cancer for precision medicine. Cancer is a heterogeneous disease, that is, it arises through a multitude of genetic mechanisms. By identifying the specific molecular and genetic lesions in cancer cells, our researchers are devising targeted approaches that take advantage of these specific lesions.
Gregory Rogers, PhD, is studying how chromosome numbers are faithfully maintained during cell division. An organelle critical to this process is the centrosome. The centrosome organizes the mitotic spindle that segregates chromatids to daughter cells at metaphase. Dr. Rogers has shown that the kinase PLK4 is a critical regulator of centromsome duplication. If PLK4 is not properly regulated, centrosomes can be over-replicated, which can lead to multi-polar segregation at metaphase and chromosome mis-segregation. PLK4 is down-regulated in many cancers, including breast and prostate cancer, and this defect may be a major cause of chromosome gain and loss so frequently observed in cancer.
Deptartment of Pharmacology Chairman Todd Vanderah, PhD, and his UACC colleagues Patrick Mantyh, PhD, JD, and Frank Porreca, PhD, have recently demonstrated the efficacy of non-psychotropic cannabinoid 2 (CB2) receptor agonists in controlling bone remodeling by metastatic breast cancer cells in a rat model. The CB2 agonist inhibits the advance of cancer cells preventing bone loss and bone pain. Dr. Mantyh has used a similar model for prostate cancer cells in the mouse to show that treatment with the compound PLX3397, which inhibits colony stimulating factor receptor-1, c-KIT, and c-FMS-like tyrosine kinase 3, can prevent the progression of bone metastasis and may reduce cancer-induced bone pain. Dr. Porecca is developing novel pain medications based on "conditioned place preference," which is an animal model that takes advantage of the rewarding nature of relief from pain.
NEW BREAST CANCER DRUGS
Joyce Schroeder, PhD, discovered that, because cancer cells lose polarity—the process that organizes epithelial cells and specifies a top and bottom of the cell—proteins come into contact with each other that are normally in separate cellular compartments. One neo-interaction in breast cancer cells that drives cancer proliferation and invasiveness is the interaction between mucin 1 (MUC1) and epidermal growth factor receptor (EGFR). Dr. Schroeder showed that she could prevent breast cancer cell proliferation and invasiveness by inhibiting the MUC1-EGFR interaction using specialized blocking peptides. These peptides are a first-in-class agent that are now being brought to clinical trials under the auspices of Arizona Cancer Therapeutics, an exciting start-up enterprise that is bringing the concept of blocking peptides to market.