Making Radioiodine Treatment a Realistic Therapeutic Opportunity in Breast Cancer
Abstract
Scientific Objective and Rationale: We hope to achieve what no other study has so far achieved: meaningful uptake of radioiodine into breast tumors and metastases. While there has been much previous published work to adapt the safe effective therapy or radioiodine treatment to breast cancer, and one previous clinical trial, no one has solved the problem of the iodide transporter NIS being located in the wrong place in breast cancer cells. NIS can only transport radioactive iodine into cells, thereby killing them, if it is located at the membrane of cells. We have now discovered a way of driving NIS to the membrane. While we have tested this in a small number of breast cancer cell lines (as well as multiple thyroid cell lines), we now need to test this thoroughly in breast cancer cells and tumors. By the end of this project, we aim to have proven whether new and existing drug treatments lead to clinically meaningful uptake of radioactive iodine into breast tumors and their metastases, hence pre-empting new and unique clinical trials for the treatment of breast cancer via radioiodine therapy. Clinical Benefit of Our Research: This application describes an entirely unique approach to treating breast cancer, and there are several attractive features of utilizing radioiodine treatment for breast tumors in terms of patient benefit. First, radioiodine treatment is well tolerated, given as a single oral dose, and is inexpensive. Side effects are usually minor and limited. Second, not all breast tumor cells need to uptake radioiodine (surrounding cells are also killed). Thus, theoretically, tumor stem cells and other difficult-to-target cell types, which often drive recurrence, should also be killed by radioiodine treatment, as well as metastases, including those in the brain. Third, radioiodine treatment is independent of hormone receptor status, and hence should work equally in triple-negative breast cancer, the most aggressive and difficult-to-treat form of breast cancer. Of course, new treatments are always needed. But this comes from a different approach: to take an established treatment in one neoplastic setting and to improve it and apply it to breast cancer therapy as an entirely separate therapy, which could offer direct hope and benefit to patients with breast cancer. How We Will Carry Out Our Investigations: We will capitalize on our entirely new data through a combination of bioinformatic, cell and animal approaches, building to direct preclinical testing of whether U.S. Food and Drug Administration-approved drugs can stimulate therapeutically relevant uptake of radioiodine into mouse breast tumors. Specifically, we will test existing drugs we have identified to increase the amount of radioiodine uptake into breast cancer cells, as well as trying to identify new ones, in order to find the very best overall drugs that stimulate radioiodine uptake. We will then examine their function in complex three-dimensional breast cancer cell cultures, before progressing to two different mouse models of breast cancer. In the first, we will transplant cells into the mice and use world-leading scanning technologies to examine whether our drugs increase radioiodine uptake into tumors and metastases. Second, and having decided upon the ultimate drug treatment, we will quantify and visualize radioiodine uptake into breast tumors induced from human breast cancers in a well understood and realistic model of breast cancer. This combination of cell experiments, drug screening, animal work and isotope visualization will, we hope, directly pave the way for new clinical trials. Which Patients: A critical part of our work will assess the levels and regulation of the NIS in breast cancer subtypes, and will use patient-derived tumor samples injected into mice. Breast cancer is a heterogeneous disease, and collectively we expect these approaches to identify whether certain patients with different breast tumor subtypes are more or les
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110554
Entities
People
- Moray J Campbell
Organizations
- Ohio State University
- United States Army