Small-molecule therapies targeting tumor-associated macrophages in glioma: mechanisms and potential

Glioblastoma, a highly prevalent and aggressive primary brain tumor, is marked by poor prognosis due to the blood-brain barrier and chemoresistance, which limit conventional pharmacotherapy. Recent research has pivoted toward targeting the tumor microenvironment, where tumor-associated macrophages (TAMs) drive gliomagenesis and malignant progression through immunosuppressive signaling. Small-molecule agents targeting TAMs have emerged as promising therapeutics, capable of reprogramming macrophage polarization, modulating immune cell dynamics, and suppressing glioma growth. This review explores the mechanistic roles of TAMs in glioma and evaluates how small-molecule compounds exert antitumor effects via TAM modulation. These insights lay a foundation for developing next-generation TAM-targeted therapies, offering significant potential for advancing macrophage-centric approaches in glioma treatment and translation to clinical practice.