Abstract P2-01-24: Sulindac and triple negative breast cancer progression

In 2018, a total of 266,120 new cases and 40,920 deaths from breast cancer in the United States were estimated by the American Cancer Society. Breast cancer is the most common malignancy and the second leading cause of death among American women. In this study, we will focus on triple negative breast cancer (TNBC), which is viewed by oncologists as a problematic and unpredictable sub-category of breast cancer because of higher rates of recurrence and poorer prognosis. TNBC accounts for up to 20% of all breast cancers and is highly prevalent in minority and young women. On average, 70% of women with metastatic TNBC die within 5 years, regardless of chemotherapy or other treatments. As such, there is an urgent medical need to develop more effective drugs to manage this deadly disease that already raised a health disparity concern, especially in the State of Louisiana. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used drugs for the treatment of pain, fever, and inflammation. Epidemiological studies have reported that the long term use of NSAIDs can prevent the occurrence multiple types of cancers, including breast cancer. However, their long term use for chemoprevention is not recommended because of toxicities associated with cyclooxygenase (COX) inhibition and the suppression of physiologically important prostaglandins. Our results show that the NSAID, sulindac sulfide (SS) and its non-COX inhibitory derivatives, can significantly inhibit the growth of the major subtypes of TNBC cells (basal-like, mesenchymal, and luminal). In addition, the compounds significantly inhibit tumor cell invasion. The animal experiments using Patient Derived Xenograft models supported the in vivo efficacy of these drugs. While studying the mechanism, we found that four oncogenic miRNAs, miR-10b, miR-17, miR-21, and miR-9 can be downregulated by SS and derivatives, and they were reported to promote tumor metastasis exclusively. Therefore, we conclude that those oncogenic miRNAs are involved in anti-metastatic activities of SS and its new non-COX inhibitory derivatives in TNBC. Citation Format: Xi Y, Yi B, Riker A. Sulindac and triple negative breast cancer progression [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-01-24.