Repurposing Anti-Depressant Imipramine for Treating Breast Cancer Patients

2024 | Vol-1 | Issue-1 | Date of Submission: | Date of Publication:

Abstract

About 1 in 8 women will develop invasive breast cancer during their lifetime, with over 41,000 deaths annually in the U.S alone. Most of these deaths are attributed to relapse, distant metastasis and therapy resistance. Unfortunately, the patients who do survive, have reduced quality of life due to the chemotherapy-associated toxicity. One mechanism that helps breast cancer to survive and become therapy-resistant is their unique ability to keep repairing their DNA. The aim of this study was to identify and test whether any FDA-approved non-cancer drug/s can block DNA repair ability and consequently growth of breast cancer cells. Treatment of breast cancer cells with a set of FDA approved drugs showed that antidepressants imipramine can inhibit the BC cell growth. Imipramine treatment significantly reduced the viability and invasive ability of TNBC and ER+ BC cells. Systemic delivery of imipramine suppressed the BC growth in preclinical mouse xenograft model. Importantly, imipramine blocked the DNA repair capacity of breast cancer cells by inhibiting the expression of DNA repair proteins including FOXM1 and RAAD51. Notably, imipramine treatment improved the efficacy of the PARP inhibitor “olaparib” in TNBC and sensitized the tamoxifen response in tamoxifen resistant ER+ breast cancer cells. Based on these results, we conducted a clinical trial in breast cancer patients that yielded highly promising results. Imipramine shows potential to be routinely used as a standalone treatment and as a therapeutic adjuvant for treating both therapy-sensitive and resistant breast cancer patients.