Abstract P4-10-29: Repurposing hypertensive drugs for breast cancer therapies

Abstract Background: Triple-negative breast cancer (TNBC) is a challenging disease to treat in patients due to a lack of well-defined molecular targets and the highly proliferative and invasive nature of these tumors. There exist several targeted therapies, but only a fraction of patients responds to these therapies and these patients typically develop resistance and relapse. The development of a new therapeutic strategy for the treatment of TNBC is desperately needed. Work in our lab has previously identified Nischarin as a potential tumor suppressor of breast cancer. The binding of Nischarin to imidazoline receptors leads to inhibition of tumor cell migration, invasion, tumor growth and metastasis. Moxonidine is a clinically approved centrally acting drug used to treat hypertension and is believed to function through imidazoline receptors. In addition, rilmenidine, a moxonidine like compound behaves the same way, and here we repurpose these drugs for breast cancer therapies. Our data for the first time show that moxonidine upregulates Nischarin expression as well as decrease tumor cell growth in vitro. In addition, rilmenidine, has also been shown to downregulate TNBC growth with a lower IC50 as compared to moxonidine. Results: Our data reveal that a dose dependent increase in Nischarin protein expression in TNBC cell line MDAMB231 treated with moxonidine as well as rilmenidine. Additionally, analysis of cell viability through MTT assays suggested that increased treatment of moxonidine or rilmenidine leads to reduced mitochondrial activity in multiple TNBC cell lines. Nischarin positive BC patients have increased overall survival (OS). We downloaded mRNA expression (level 3RNAseq v2) and survival information for 921 patients with breast invasive carcinoma from TCGA portal. In addition, publicly available RNAseq data from TCGA suggests decreased Nischarin expression in TNBC as compared to other breast cancer subsets (LumA, LumB and normal tissue). These data suggest that Nischarin expression is low in TNBC, and it is important to induce the expression in TNBC. Conclusions: Triple-negative breast cancer is an incredibly deadly subset of a highly heterogenous disease. These tumors are highly refractory to clinically approved therapies due in part to their highly proliferative and metastatic capabilities. Nischarin has been shown to downregulate the proliferation of cancer cells as well as inhibit their metastatic potential. Using clinically approved hypertensive drugs moxonidine and rilmenidine as drugs to regulate TNBC tumor development by increased Nischarin expression can serve as a fundamental basis for a novel new therapeutic strategy. Citation Format: Maninder Khosla, Shengli Dong, Suresh K. Alahari. Repurposing hypertensive drugs for breast cancer therapies [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-10-29.