The Role of Traditional Chinese Medicine in Metabolic Reprogramming, Tumor microenvironment, and Macrophage Regulation: Mechanisms and Advances in Preclinical Studies.

Abstract

Background: Cancer metabolism reprogramming is a hallmark of tumorigenesis, playing a critical role in tumor progression and therapeutic resistance. Macrophages in the Tumor microenvironment (TME) play a crucial role in tumor progression and immune system evasion. Traditional Chinese Medicine (TCM) has shown potential in influencing cancer metabolism and immune functions, offering new therapeutic possibilities.

Objective: This review explores the intersection of TCM, metabolic reprogramming, and macrophage polarization in cancer, focusing on their molecular mechanisms and therapeutic implications. The study further seeks to summarize preclinical evidence supporting TCM's role in modulating tumor metabolism and immune microenvironments, offering a holistic approach to cancer therapy.

Methods: In this study, we systematically reviewed the latest research progress in the last five years on the role of traditional Chinese medicine in regulating tumor metabolic reprogramming, TME and macrophage polarization. A comprehensive literature reviews the metabolic shifts in cancer cells, including glycolysis, oxidative phosphorylation, and lipid metabolism, and how TCM compounds restore metabolic balance. Studies on macrophage polarization (M1/M2) and their regulatory roles in cancer immunity, as influenced by TCM, were analyzed. Preclinical research highlighting TCM's dual impact on tumor metabolism and the TME was also evaluated.

Results: TCM compounds demonstrate the ability to target key metabolic pathways, such as glycolysis and lipid metabolism, restoring metabolic homeostasis in cancer cells. Additionally, TCM has been shown to regulate macrophage polarization within the TME, enhancing M1 macrophage-mediated anti-tumor immunity and suppressing M2 macrophage-mediated tumor promotion. Preclinical studies further support TCM's capacity to modulate the TME and improve therapeutic outcomes when used in combination with conventional cancer therapies.

Conclusions: TCM integrates metabolic reprogramming and immunomodulation to provide a comprehensive treatment strategy for cancer. However, translating these findings into clinical practice remains challenging. Future research should focus on validating the exact mechanisms of TCM in tumor metabolism and immunity through clinical trials and investigating the synergistic effects of TCM with modern cancer therapies, such as immunotherapy and targeted therapies. This may facilitate the use of TCM as an adjuvant therapy to improve the efficacy of existing cancer treatments.