Plant-Derived Diterpenoids as Potential Chemotherapeutics for Gastric Cancer.

PURPOSE OF REVIEW: Gastric cancer remains a leading contributor to cancer-related mortality worldwide despite its declining incidence, with poor survival rates. Standard treatments, such as surgical resection, radiotherapy, chemotherapy, and immunotherapy, often achieve limited success, underscoring an urgent need for the development of novel and effective treatment strategies. Plant-derived diterpenoids demonstrate a wide range of bioactivities including antitumor activity. The aim of this review is to compile, integrate, and discuss the latest information concerning plant-derived diterpenoids with anti-gastric-cancer activities.

RECENT FINDINGS: In this review, we mainly summarize current knowledge on the anticancer effects of plant-derived diterpenoids against gastric cancer, with a focus on their underlying molecular mechanisms, such as induction of apoptosis, modulation of reactive oxygen species, inhibition of metastasis, and chemotherapy sensitization, based primarily on preclinical evidence from in vitro and in vivo experimental evidence, with human clinical data available only for paclitaxel. Among the diterpenoids reviewed, carnosol, triptolide, and paclitaxel demonstrate the most robust preclinical evidence, supported by patient-derived xenograft models, direct target identification, or clinical validation. We also analyze the realistic challenges in translating these plant-derived diterpenoids into clinical practice. We conclude from this review that plant-derived diterpenoids demonstrate anticancer activity against gastric cancer in preclinical models through various pharmacological mechanisms. This review highlights that these key mechanisms are mediated by distinct pharmacological pathways, that most evidence is derived from in vitro and animal studies, and that clinical relevance remains limited. These insights may inform future research aimed at therapeutic development.