# Natural Products in Cancer Prevention and Therapy: Current Challenges and Future Directions

## TL;DR

Natural products offer cancer prevention and treatment by targeting metabolism and the tumor environment, with new delivery methods improving their effectiveness.

## Contribution

This review systematically outlines how natural products target metabolism and the tumor microenvironment across all clinical phases of cancer care.

## Key findings

- Natural products modulate glucose, lipid, and glutamine pathways in cancer cells.
- They influence tumor-associated macrophages and T lymphocytes in the tumor microenvironment.
- Innovative delivery systems like nanocarriers enhance the bioavailability and synergy of natural products with other therapies.

## Abstract

Natural products, originating from diverse biological sources, serve as a critical reservoir of bioactive compounds for cancer intervention across prevention, treatment, and supportive care. Their mechanisms extend beyond direct cytotoxicity to include modulation of tumor metabolism—such as glucose, lipid, and glutamine pathways—and the tumor microenvironment (TME), highlighting their multifaceted role in oncology. However, a systematic synthesis of how natural products concurrently target metabolic reprogramming and immune–stromal components across different clinical phases remains lacking. This review delineates the therapeutic applications of natural products—such as flavonoids, alkaloids, and terpenoids—across the clinical continuum, including perioperative support, concurrent chemoradiotherapy, maintenance therapy, and metastasis suppression. We detail their actions in disrupting core metabolic pathways and elucidate their influence on TME components like cancer‐associated fibroblasts, extracellular matrix, and immune cells including tumor‐associated macrophages and T lymphocytes. Furthermore, we discuss innovative delivery strategies—including nanocarriers and codelivery systems—that enhance bioavailability and enable synergistic combination with chemotherapy or immunotherapy. By integrating mechanistic insights with clinical translation strategies, this work provides a comprehensive framework for employing natural products in biomarker‐driven, precision oncology regimens, supporting their evolving role in multimodal cancer care.

Natural products play a pivotal role in cancer therapy. They induce cancer cell death by reprogramming four metabolic pathways while precisely targeting the tumor microenvironment and immune cells. These compounds not only leverage novel delivery systems for innovative applications but also demonstrate unique therapeutic efficacy across clinical stages: primary prevention, concurrent treatment phase, postoperative recovery, maintenance therapy, and end‐of‐life care.