The ASPIRE Path in Molecular Medicine

For my thesis work, I plan on investigating resistance mechanisms to the antibody trastuzumab in HER2-positive breast cancer. Patients who have HER2 breast cancer will typically take trastuzumab for a year after receiving initial chemotherapy and/or surgery. Trastuzumab has shown to be vital in reducing the risk of recurrence and prolonging survival. One mechanism through which trastuzumab works to kill cancer cells is antibody dependent cellular cytotoxicity (ADCC). ADCC occurs when antibodies bind to antigens on the surface of a target cell, marking it for destruction by immune cells, including natural killer (NK) cells. NK cells can recognize the antibody-coated target cell through their Fc receptors, releasing cytotoxic substances that can lead to cell lysis. It is thought that this process is vital for tumor killing in HER2 breast cancer. Thus, I hope to explore if resistance to ADCC is one mechanism that drives tumor progression in these patients. Ultimately, I would love to use publicly available patient data to explore tumor samples and associated NK cell data to see if there are certain NK cell properties that make patients more susceptible to recurrence. If so, is it possible to target these NK cells to help “rejuvenate” ADCC killing?