Itraconazol, an Antifungal and a Hedgehog Pathway Inhibitor for Treatment of Prostate Cancer
Abstract
It was recently observed that a commonly used antifungal, Itraconazol, targets a pathway that is also upregulated in human prostate cancer. It was also observed that Itraconazole synergizes with cyclopamine to induce superior therapeutic effects. Cyclopamine is toxic; however, when combined with itraconazole, the dose requirement for each drug was considerably reduced. This combination therefore has the potential to be more effective and at the same time less toxic. The most important aspect of this finding is that these are existing drugs whose safety and toxicological profiles are known. Another important feature is that in combination with other known inhibitors, the effective dose of each individual drug is drastically reduced, thus reducing the possibility of adverse side effects. The data obtained will provide information on the usefulness of these inhibitors against advanced prostate cancer that can be further validated in appropriate preclinical models of human prostate cancer and take it a step closer to being tested in humans. The efficacy of itraconazole will be tested in combination with cyclopamine against prostate cancer cell lines and also on normal prostate cells. This will be followed by developing animal models of drug testing such as the nude mouse model. The effect of the drugs will be tested on proliferative, tumorigenic, and metastatic potential. This application is designed to investigate the efficacy of Itraconazol against prostate cancer with an intention to accelerate its rapid translation into human clinical trials. This proposal is likely to identify a combination of drugs for the treatment of advanced prostate cancer. These are preclinical studies; however, if the efficacy of the drug can be established against prostate cancer in this proof-of-principle study, then clinical trials could be immediately started based on the fact that these are existing drugs with all the information about toxicity and dose. The drugs therefore do not have to undergo the mandatory initial trials to establish dose and toxicity.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510513
Entities
People
- Hasan Mukhtar
Organizations
- United States Army
- University of Wisconsin–Madison