Abstract LB-481: MicroRNAs as novel therapeutic targets to treat drug-resistant breast cancers

Abstract

Abstract Acquired drug resistance continues to be a major clinical impediment to the successful treatment of cancer. For example, resistance to agents such as paclitaxel and trastuzumab accounts for treatment failure in more than 90% of patients with metastatic breast cancers. Understanding the mechanisms underlying such resistance is therefore crucial for the development of new, efficacious drugs against cancer. Unfortunately in spite of extensive inquiry in this field, little is known about the key molecules and signaling pathways that regulate this phenomenon. Recently, we have discovered that microRNAs (miRNAs) may play critical roles in mediating drug sensitivity/resistance in breast cancers. We have identified miRNAs that are differentially expressed between chemo-resistant and sensitive HER2+ breast cancer cells. Specifically, through high-throughput miRNA inhibitor library screens, we have identified miRNAs that sensitize drug-resistant breast cancer cells to paclitaxel and trastuzumab, a drug combination commonly used for the treatment of metastatic HER2+ breast cancers. MiRNA/s that alter/s the cellular response to these drugs may target a common signaling pathway. For example, resistance to paclitaxel/trastuzumab in breast cancer has been proposed to be a consequence of loss of PTEN expression, leading to altered AKT signaling. Our findings suggest that certain miRNAs are selectively cytotoxic in a drug-specific manner and that these miRNAs may provide novel adjuvant therapeutic tools for the treatment of drug-resistant metastatic breast cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-481. doi:1538-7445.AM2012-LB-481