Systemic Efficacy of Sirolimus via the ERBB Signaling Pathway in Breast Cancer

Abstract

Rapamycin, also known as sirolimus, inhibits the mTOR pathway in complex diseases such as cancer, and its downstream targets are ribosomal S6 kinases (RPS6K). Sirolimus is involved in regulating cell growth and cell survival through roles such as the mediation of epidermal growth factor signaling. However, the systemic efficacy of sirolimus in pathway regulation is unclear. The purpose of this study is to determine systemic drug efficacy using computational methods and drug-induced datasets. We suggest a computational method using gene expression datasets induced by sirolimus and an inverse algorithm that simultaneously identifies parameters referring to gene–gene interactions. We downloaded two sirolimus-induced microarray gene expression datasets and used a computational method to obtain the most enriched pathway, then adopted an inverse algorithm to discover the gene–gene interactions of that pathway. In the results, RPS6KB1 was a target gene of sirolimus and was associated with genes in the pathway. The common gene interactions from two datasets were a hub gene, RPS6KB1, and 10 related genes (AKT3, CBLC, MAP2K7, NRG1/2, PAK3, PIK3CD/G, PRKCG, and SHC3) in the epidermal growth factor (ERBB) signaling pathway.