The University of Arizona Cancer Center’s Therapeutic Development Program, led by Robert T. Dorr, PhD, RPh, works to discover new biological targets and develop agents that will translate into life-changing therapies that efficiently and effectively treat cancer. Program Project Grant: Therapeutic Targeting of Hypoxic and Oxidative Stress (5P01 CA017094-33; P.I.: Robert Dorr, Ph.D.) (Renewed 2007)
The Program oversees all stages of therapeutic discovery and development, from laboratory-based discovery and development to early-stage translational clinical trials. The Therapeutic Development Program relies on a close interaction between basic researchers and clinical investigators, ensuring a seamless translation of laboratory discoveries into clinical settings.
The Therapeutic Development Program is leading cutting-edge studies to identify promising molecular and genetic targets to get us closer to the day when all cancer treatments are tailored to each individual patient. Additionally, the Therapeutic Development Program aims to improve the quality of life of patients undergoing treatment by seeking therapies to reduce the occurrence of common cancer-related conditions, such as bone pain and metastasis.
The Lymphoma Team, headed by Tom Miller, MD, and Lisa Rimsza, MD, tested a new agent that works through oxidation in patients with non-Hodgkin's lymphoma that are not responsive or have relapsed after other therapies. The agent, imexon, is a small molecule that causes tumor cells to become oxidized and die. The clinical trial produced an overall response rate (tumor shrinkage) in 30 percent of patients, and 35 percent of tumors stopped growing.
Program members have identified unique new targets for drug development that involve special structures in cancer DNA. These targets, called i-motifs, are "twists" in DNA strands that occur in sections of DNA that activate cancer genes. Importantly, these i-motifs have been shown to control how cancer genes are both turned on (leading to cancer) and off (inhibiting cancer). The team, led by Laurence Hurley, PhD, and Danzhou Yang, PhD, has used this to model to develop new drugs.
In many tumors, the majority of cells in the tumor mass have low oxygen levels (hypoxia), which makes these cancer cells highly resistant to both drugs and radiation. Amanda Baker, PhD, PharmD, and Marty Pagel, PhD, have joined forces to address these cells. Dr. Pagel is developing imaging techniques that can spot tumors that are acidic (and therefore are also hypoxic). Dr. Baker is working with agents like the experimental drug TH 302, that are activated only in hypoxic conditions.