Arizona-based Systems Oncology has licensed a patented drug compound from the University of Wisconsin-Milwaukee Research Foundation. The compound employs a unique mechanism of action that has safely and effectively suppressed tumors in animal models. Specifically, the compound changes a transcription reprogram in tumor cells. Transcription is the process of turning specific genes on. Groups of genes can be turned on or off together as a transcriptional program that regulates a cell's behavior.
Dr. Alexander Arnold, an associate professor of chemistry and biochemistry, discovered novel small molecules that can disrupt the interaction between the vitamin D receptor (VDR) and other proteins that regulate transcription.
When VDR binds to the activated form of vitamin D, it drives a transcriptional program for proper cell growth and differentiation. Local degradation of the active form of vitamin D may lead to uncontrolled cancer growth, and malignant remodeling of the tumor microenvironment, which is the environment in and around the tumor. This makes tumors less likely to respond to cancer drugs and cancer immune-therapy.
"Initial studies suggest that new drug candidates that bind the VDR can be a safe and effective therapy for some difficult to treat cancers," Arnold said. "By using these newly discovered molecules we can target the regulation of VDR genes."
But VDR also is the "master regulator" of calcium in the body.
Several new anti-cancer drugs in clinical trials are based on vitamin D, but they may disrupt the body's vital levels of calcium over time. More importantly, cancer cells over-express proteins that inactivate the active form of vitamin D in the microenvironment of a tumor, reducing the efficacy of such therapies.
Arnold's compounds alter the VDR's action selectively, and block the local inactivation of vitamin D around the tumor microenvironment, without interfering with the systemic calcium regulation needed for normal health.
Systems Oncology LLC is a machine learning-based biotechnology company that uses cognitive computing and multi-scalar systems modeling to mine massive datasets and uncover hidden therapeutic insights for cancer.
Dr. Spyro Mousses, the company's CEO, said his team recognized the tremendous therapeutic opportunity in the VDR mechanism discovered by Arnold and can clinically position the cancer therapy for rapid approval.
"Dr. Arnold and his team created a truly excellent small molecule compound. Our modeling work suggests that the compound's unique mechanism of action has the potential to transform how we manage some of the toughest cancer types. We are excited to have the opportunity to work with pharmaceutical co-development partners to translate this important new agent into a breakthrough cancer therapy," Mousses said.
The UWM Research Foundation, a nonprofit corporation that provides research, entrepreneurship and innovation programs at UWM, has supported Arnold's research and helped to commercialize it.
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