Grant: Operating Grant

Breast cancer (BC) is a heterogeneous disease that can be divided into different subtypes based on evaluation of specific markers on BC cells. Human epidermal receptor 2 (HER2) is one of the markers that is commonly evaluated for subtype identification. HER2 positive (HER2+) BC is associated with a significantly worse prognosis than HER2- BC and increased risk of recurrence and death. Approximately 15-30% of BC cases are reported to be HER2+. The introduction of the HER2 targeted therapy, trastuzumab, administered in combination with effective chemotherapies such as docetaxel has transformed treatment for patients with HER2+ disease resulting in significant improvements in overall outcomes. However, once patients develop metastatic BC there are not curative options and the disease will eventually progress in all patients. Indeed, it is the development of trastuzumab resistance that remains a significant therapeutic challenge. The proposed research directly addresses this clinical challenge through the development of powerful new nanotechnology which has been engineered to deliver Indium-111 as radiotherapy and docetaxel as chemotherapy specifically to trastuzumab resistant HER2+ BC cells. This research builds on recent clinical data that show that targeting of a cytotoxic agent to HER2+ trastuzumab resistant tumours can overcome resistance. In our proposed treatment strategy we use pharmaceutically safe materials to deliver the cytotoxic agents, Indium-111 and docetaxel, for the selective killing of HER2+ BC cells, as a potent combination therapy.