SRA

Breast cancer is the most common cancer in women and the leading cause of cancer-related deaths in women worldwide. Although survival of breast cancer patients has improved in the last decade, major hurdles remain. Two problems associated with current therapies include acquired resistance and the debilitating side effects of treatment, especially chemotherapy. Therefore, safer treatment options that effectively suppress cancer progression and reduce treatment-associated side effects are much needed. Repurposing of clinically approved or investigational drugs could be one type of effective and safe options for treating cancer patients. Imipramine is a tricyclic antidepressant commonly used for many decades. It is a selective serotonin reuptake inhibitor (SSRI) and inhibits other neurotransmitters. Here, we report that imipramine blocks ER+ and TNBC growth and progression by inhibiting key proteins involved in ER-a signaling, cell cycle progression, and DNA repair and replication. Furthermore, imipramine improved the efficacy of PARP inhibitor therapy in TNBC. This study is the first to show that imipramine is a promising therapeutic option for breast cancer and to define imipramine's mechanism of action and targets in breast cancer. This pre-clinical study is the basis for a currently ongoing clinical trial testing the efficacy of imipramine for treating breast cancer. Overall design: Total RNA from MCF7 and MDA-MB-231 vehicle or imipramine-treated cells were isolated using RNeasy mini kit (Qiagen). Each sample were replicated and sequenced using Illumina TruSeq RNA Sample preparation and sequencing protocols at UT Health San Antonio sequencing facility.