Combination Nitazoxanide and Auranofin Treatment for Anaplastic Thyroid Cancer
Abstract
Anaplastic thyroid cancer is a rare (incidence of one to two cases per million persons per year) and deadly cancer. No current treatment regimen results in long-term shrinkage of the cancer and thus, no current treatment cures patients or prolongs their life. Given this, we have used high-throughput drug screening of already clinically approved or investigational drugs to identify candidate new drugs that could be repurposed for anaplastic thyroid cancer treatment. Because single drug treatment for most cancers is not effective long-term, we also used combination drug screening of those compounds that had high activity for killing anaplastic thyroid cancer cells from our high throughput drug screening studies. One of the combination with the highest activity of killing anaplastic thyroid cancer cells in preclinical models was combination nitazoxanide and auranofin treatment. This combination treatment also altered the protein levels of two molecules (glutathione Peroxidase 4, heme oxygenase-1) in anaplastic thyroid cancer cells. What remains unknown are the preclinical safety, optimal doses of combination nitazoxanide and auranofin treatment, and whether the two molecules could be used for determining treatment response. Thus, this proposal directly addresses a Focus Area for fiscal year 2022 Rare Cancers Research Program, as it will evaluate a new combination treatment strategy (combination nitazoxanide and auranofin treatment) and the idea of repurposing of drugs in use for other indications for a rare cancer (anaplastic thyroid cancer). In this proposal, we will evaluate the safety and anticancer activity of combined nitazoxanide and auranofin treatment in preclinical models of anaplastic thyroid cancer and will determine if two molecules are associated with response to combination nitazoxanide and auranofin treatment in preclinical models of anaplastic thyroid cancer. The rationale for performing these experiments is our promising preliminary data, and that (1) its successful completion will significantly contribute to the translation of this novel treatment combination into the clinic for patients with anaplastic thyroid cancer, and (2) allow the selection of cancers that could be treated with this regimen and could help determine early treatment response. We anticipate the project will take 2 years to complete and that it will lay the foundation for moving this treatment to the clinic quickly for patients with anaplastic thyroid cancer. This is because both drugs have been in clinical use for decades for rheumatoid arthritis (auranofin) and parasite infections (nitazoxanide) and their effect and toxicity, which are minimal when used alone, is well known in the human body. Upon successful completion of the proposed research, we expect to have shown dose ranges that could be safely used for optimal anticancer treatment and confirm the accuracy of the two molecules that can predict treatment response in comprehensive preclinical models that mimic the aggressiveness of anaplastic thyroid cancer. This contribution will be significant because it will represent an important next step toward establishing a new treatment for a rare and deadly cancer. Further, our findings will allow this combination treatment strategy using nitazoxanide and auranofin to be rapidly translated to the clinic to conduct clinical trials in humans with anaplastic thyroid cancer. Moreover, combined nitazoxanide and auranofin treatment for other rare cancers could also be considered in the future based on the results from this research proposal, which would be an advance for rare cancer research.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310625
Entities
People
- Electron Kebebew
Organizations
- Stanford University
- United States Army