Grant: Master's Award: Canada Graduate Scholarships

Breast Cancer is the most common form of malignant cancer in women. Globally, there were an estimated 2.3 million new cases of breast cancer in 2022, demonstrating the need for an improved method of treatment. Radiation therapy is an effective treatment modality, however radiation resistant cells can develop resulting in therapy resistant cancers. These cells severely increase the difficulty in treating breast cancer, as it removes the option to use radiation therapy to target the location where the cancer is located. Our lab hopes to identify the molecular mechanisms for treating radiation resistant breast cancer. Triple negative breast cancer is a form of therapy resistant breast cancer that is characteristic of lacking three common surface receptors: estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. By using the triple negative breast cancer cell line MDA-MB-231, previous students on this project were able to create a radiation resistant breast cancer cell line that we will be using for this project. After performing RNA sequencing on the radiation resistant cell line, one target that was found to be upregulated (by sixteen-fold) was cyclooxygenase-2 (COX2). This is an enzyme involved in converting arachidonic acid into prostaglandins to initiate the inflammatory response. We hypothesize that COX2 upregulation may be increasing radiation resistance in our MDA-MB-231 cells, and by downregulating the expression of this enzyme, radiation sensitivity will increase. We plan to downregulate COX2 activity using pharmacological inhibitors. In summary, the objective is to determine whether COX2 is an underlying mechanism in radiation resistance, and if COX2 inhibition is a druggable target for therapy resistant breast cancers.