Dual-cancer mechanism of Berberine reversal of chemoresistance by targeting the three-dimensional barrier of tumor microenvironment: a systematic review of colorectal and triple-negative breast cancers

Abstract

Chemoresistance in colorectal cancer (CRC) and triple-negative breast cancer (TNBC) is an insurmountable problem in clinical treatment, and its core mechanism is closely related to the three-dimensional "stroma-metabolism-immunity" barrier formed by the tumor microenvironment (TME). Berberine (BBR), a natural isquinoline alkaloid, can regulate the TME from a multi-target perspective, but its synergistic mechanism across cancer types and its clinical translational pathway have not been systematically elucidated. In this paper, we integrated the preclinical studies of CRC and TNBC to reveal that BBR reshapes the interactions network by targeting shared hub targets such as PI3K/AKT and STAT3, and breaks the TME barrier through metabolism-immunity cross-regulation, and further proposed the optimization of targeted delivery system, translational medicine framework, which provides theoretical basis and clinical translational ideas for BBR to reverse the chemoresistance of dual-cancer species.