Triptolide in the Treatment of Lung Cancer

Today, Lung cancer is the cancer with the highest fatality rate worldwide,which seriously affects physical and mental health. Due to the inadequacy of existing treatment methods, people have launched extensive research on new drugs with potential for cancer treatment. Triptolide, a diterpenoid epoxide derived from Tripterygium wilfordii, has emerged as a promising multi-target agent against lung cancer. This review systematically summarizes triptolide's mechanisms including: (1) proliferation inhibition via HnRNPA2/B1-PI3K/AKT suppression; (2) apoptosis induction through mitochondrial (SIRT2/p53/Bcl-2/Bax) and cuproptosis (ATP7A/B-DLAT oligomerization) pathways; (3) Wnt/-catenin signaling blockade by p70S6K/GSK-3 inhibition; (4) immunomodulation via Stat3/NF-B axis. Despite demonstrating potent anti-tumor efficacy in preclinical models, clinical translation is hindered by its narrow therapeutic window (hepatorenal toxicity) and poor bioavailability. Recent advances in structural derivatives (e.g., Omtriptolide) and drug combinations (e.g., with cisplatin) show potential for overcoming these limitations. Further optimization of toxicity profiles and pharmacokinetics is essential for advancing triptolide into Phase II trials.