Understanding the complexity of tumor-associated macrophages: Druggable and therapeutic insights.
10.1016/j.apsb.2025.07.021
- Author:
An-Qi LI
1
;
Fang HUANG
1
;
Sulaiya TALAITI
1
;
Xiao YANG
1
;
Huichang BI
1
;
Jian-Hong FANG
1
Author Information
1. NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
- Publication Type:Review
- Keywords:
Drug development;
Heterogeneity;
Precision medicine;
Single-cell omics;
Targeted therapy;
Tumor immunity;
Tumor microenvironment;
Tumor-associated macrophages
- From:
Acta Pharmaceutica Sinica B
2025;15(9):4456-4475
- CountryChina
- Language:English
-
Abstract:
Macrophages are immune cells capable of exerting both pro-tumor and anti-tumor effects. Tumor-associated macrophages (TAMs) comprise a heterogeneous group of macrophages originating from monocytes and resident tissue macrophages. Their phenotypes and functions vary depending on factors such as tumor type, location, and stage. TAMs can promote tumor growth, angiogenesis, metastasis, immunosuppression, and drug resistance, or they can facilitate antigen presentation and immune activation, thereby contributing to tumor elimination. As such, TAMs are potential targets for cancer therapy, and various pharmacological strategies and clinic-approved drugs have been suggested to modulate their activity, recruitment, and depletion. However, the complexity and diversity of TAMs present significant challenges to understanding their roles and designing effective drug interventions. This review summarizes the current knowledge of TAMs, and drug development for TAMs as anti-tumor therapy targets, emphasizing the importance of single-cell omics technologies for characterizing TAM heterogeneity and identifying therapeutic opportunities. Additionally, it presents the latest clinical trials focused on TAM-targeted therapies and drugs. Collectively, this review discusses the therapeutic opportunities and challenges of TAM-targeted drug therapies and offers future perspectives and directions for advancing our understanding and manipulation of TAMs in drug development.
