OPPORTUNITY

The role of developmental pathways such as the Hedgehog pathway has been studied for its involvement in several malignancies. The Hedgehog pathway activates signaling in cancer cells that causes them to proliferate, survive and be more aggressive. The Hedgehog pathway can be inhibited by small molecule inhibitors. Several of these inhibitors have been developed and some are being tested in clinical trials. While treatment with Hedgehog inhibitors usually involves injections to make the drug available systemically, monitoring of the efficacy of drug treatment is usually by assessing tumor regression or by disease-free survival. Ideally, a marker of treatment response and efficacy could be measured and monitored to ensure that the right patient the right drug.

BREAKTHROUGH IN CANCER DIAGNOSIS AND THERAPY

Inventors at the University of South Alabama have identified a positive correlation between Hedgehog pathway and Osteopontin expression levels using both melanoma cell culture and human tumor samples. Expression levels of Osteopontin increase with the development and progression of melanoma. Inventors have discovered that the Hedgehog pathway regulates the oncoprotein, Osteopontein by transcriptionally upregulating it. GLI1, a component of the Hedgehog pathway, can be effectively inhibited by shRNA in vitro. GLI1 inhibition by shRNA results in decreased Osteopontin expression levels which may result in the prevention or delay of progression of melanoma. In fact, research from the University shows that inhibiting the Hedgehog pathway can reduce melanoma tumor growth as well as reduce metastasis in an animal model of human cancer (pre-clinical model). In addition, data show that the Hedgehog pathway plays a critical role in allowing breast cancer cells to metastasize to the bone. Inventors have demonstrated that Osteopontin plays a pivotal role in governing the behavior of cancer cells and also that of cancer stem cells. Since, Osteopontin levels correlate with the Hedgehog pathway, Osteopontin could be used as a surrogate biomarker to evaluate the efficacy of Hedgehog inhibitors or GLI1 shRNA. In addition, Osteopontin levels could be used as a marker to predict response to these treatments.

COMPETITIVE ADVANTAGES

•  Identify which patients may respond to therapy

•  Monitor therapeutic efficacy

•  Diagnostic marker with a drugable target

INTELLECTUAL PROPERTY STATUS

Patent filed