Natural Products Targeting the Tumor Microenvironment: A Comprehensive Overview of Colorectal Cancer Therapeutics

Colorectal cancer poses a significant clinical challenge, with an alarming annual incidence of nearly 1.88 million new cases and limited therapeutic strategies, especially for advanced stages. The tumor microenvironment represents a complex ecosystem encompassing tumor cells, immune cells, cancer-associated fibroblasts, and extracellular matrix. This ecosystem is pivotal in orchestrating the trajectory of colorectal cancer evolution and can be divided into six microenvironments: acidic, hypoxic, metabolic, immune, microbiota, and stromal. The tumor microenvironment has increasingly garnered attention in oncological research, as modulating these environments presents novel therapeutic avenues for colorectal cancer. This review provides a comprehensive evaluation of the capacity of natural products to modulate the tumor microenvironment and augment colorectal cancer therapeutic outcomes. Additionally, this review underscores seminal clinical and preclinical studies, providing valuable insights to unlock the full potential of natural products in the development of novel drugs to effectively address the challenges posed by colorectal cancer.