Natural Products in Cancer Research: Mechanistic Advances, Translational Challenges, and the Emerging Role of Chilean Biodiversity

Natural products have long contributed to oncology by providing structurally diverse metabolites and pharmacologically relevant scaffolds. Despite advances in precision oncology, immunotherapy, and targeted therapies, cancer remains a leading cause of morbidity and mortality worldwide. Plant-derived metabolites continue to attract attention due to their ability to modulate key processes such as apoptosis, metabolic adaptation, epigenetic regulation, oxidative stress, inflammation, and tumor microenvironment signaling. However, current evidence is heterogeneous and often based on simplified in vitro models or insufficiently characterized extracts. This review critically distinguishes pharmacologically validated findings from preliminary claims with limited translational relevance. A narrative synthesis of global advances was conducted, focusing on mechanistic pathways, major phytochemical classes, and emerging technologies shaping compound discovery and preclinical validation. The potential contribution of Chilean biodiversity was also examined. Although several Chilean plant species demonstrate cytotoxic, anti-inflammatory, and antioxidant activities relevant to oncology, most findings remain preclinical, limited by inadequate taxonomic identification, lack of phytochemical standardization, scarce in vivo validation, and insufficient pharmacological characterization. The future impact of natural products on oncology will depend on stricter standards for chemical characterization, biological validation, and translational relevance. Chilean biodiversity represents a promising yet largely prospective source for cancer-related drug discovery.