Metastatic disease is responsible for most breast cancer deaths. Surgery is ineffective in removing these lesions, and the toxic effects of many chemotherapeutics make them less desirable. Novel therapies are attempting to decrease side effects by targeting the drugs to specific biomarkers expressed in cancer cells, but this approach is only effective in a subgroup of breast cancer patients, requiring the use of combination therapies that eventually lead to multidrug resistance. Equally troubling is the frequent relapse of cancer in patients that were considered to be cancer-free. Immunotherapy could combat cancer relapse, but recent excitement about the successful use of this approach to combat lung cancer and melanoma has not fully translated to breast cancer because of the active suppression of immune cells in breast cancer environment.

In this proposal, we aim to develop a new strategy that increases treatment efficacy, prevents cancer relapse, and minimizes the toxic effects of drugs to healthy tissue. Our approach will transform poisonous or ineffective chemotherapeutics into safe and efficient drugs through a novel treatment paradigm, stimulated intracellular light therapy (SILT). SILT will employ nontoxic (low) doses of drugs and radioisotopes that are routinely used in clinics to selectively induce direct cancer cell death by generating localized toxic radicals, followed by activating the immune system to eradicate residual cancer cells. The unique ability to control when and where cell death will occur provides a unique strategy to stimulate therapy at the appropriate time. SILT will destroy cancer cells gradually, thus avoiding the overloading of the body with dead cells, which could trigger an autoimmune response.

Because the initial cell death mechanism does not rely on inhibiting a particular type of signaling pathway, SILT will be applicable to different breast cancer types, including hormone-responsive, hormone-refractory, and triple-negative breast cancer. Light-based therapies are not known to induce therapy resistance. Therefore, SILT can also be used to prevent cancer relapse or the onset of new cancer in high-risk subjects. By repurposing some current clinically used radiopharmaceuticals and drugs for the new treatment paradigm, we anticipate a rapid clinical translation of this research.