Exploring combinations of dihydroartemisinin for cancer therapy: A comprehensive review

Abstract

Cancer remains a significant threat to human health due to its multifaceted causes and complex pathogenesis. While advancements in research have improved outcomes for many cancer patients, treatments for specific tumor types still face limitations. Dihydroartemisinin (DHA), an active metabolite of artemisinin and its derivatives, has proven to be an effective anti-malarial agent. Recently, its anticancer potential has garnered increasing interest as it acts through multiple molecular pathways, including anti-proliferation, induction of apoptosis, autophagy and endoplasmic reticulum (ER) stress, anti-metastasis, inhibition of angiogenesis, and modulation of immune function. This review aims to thoroughly explain and summarize the mechanisms of DHA against cancer and the latest progress in this field. Due to the insufficiency of monotherapy in effectively treating cancer, the use of chemotherapy in combination with alternative therapies has witnessed a notable increase in popularity. DHA has shown synergistic anti-tumor efficacy with a range of therapeutic drugs, but its co-delivery with chemotherapeutics has been limited by low solubility and bioavailability. Nanotechnology-assisted co-delivery of anti-tumor agents, utilizing advanced stimulus-triggered drug release systems in tumor cells, offers the potential to enhance selective delivery and increase antitumor efficacy. Additionally, this article provides suggestions for further research on the anticancer effects of DHA. © 2025 Elsevier Inc.