Triple-negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer and often does not respond well to available treatments. Unlike other breast cancer types, TNBC lacks common targets for therapy and has limited treatment options beyond chemotherapy. One promising approach is immunotherapy, which capitalizes the body’s immune system to recognize and attack cancer cells. However, many TNBC tumors do not respond to currently available immunotherapies because they fail to present enough tumor-specific signals (or neoantigens) on their surface that can be detected by immune cells. Our research focuses on a newly recognized source of these neoantigens. Our team found that...
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Triple-negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer and often does not respond well to available treatments. Unlike other breast cancer types, TNBC lacks common targets for therapy and has limited treatment options beyond chemotherapy. One promising approach is immunotherapy, which capitalizes the body’s immune system to recognize and attack cancer cells. However, many TNBC tumors do not respond to currently available immunotherapies because they fail to present enough tumor-specific signals (or neoantigens) on their surface that can be detected by immune cells. Our research focuses on a newly recognized source of these neoantigens. Our team found that certain genetic changes in TNBC tumors cause the cells to incorrectly process their RNA, creating abnormal sequences that when translated, can give rise to neoantigens. As these neoantigens are absent in normal cells, they have the potential to alert the immune system and induce tumor cell killing while limiting side effects. However, many neoantigens are blocked from production because their RNA remains trapped inside the nucleus of the cancer cell. We aim to solve this problem in two ways. First, we will identify which of these neoantigens are shared across different TNBC tumor cells and can be efficiently recognized by immune cells. This will make immunotherapy a viable treatment option for more patients with TNBC and potentially other cancers with similar genetic features. Second, we will test FDA-approved drugs to find those that help export aberrant RNAs from the nucleus into the cytoplasm, allowing the neoantigens to be produced and presented to the immune system. This will pave the way for new cancer therapies that unmask hidden neoantigens, making tumors visible to the immune system and treatable through next-generation immunotherapies.
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