Cephalotaxus-Derived Homoharringtonine: Biosynthesis, Mechanism of Action, and Role in Modern Cancer Therapy

Abstract

The naturally occurring Cephalotaxus species belonging to the Cephalotaxaceae family have been investigated due to the unique characteristics of their secondary phytometabolites with diverse biological activity. These metabolites have been isolated and used in different Chinese medicines for the treatment of different diseases, specifically for leukemia. However, the knowledge gap of relevant metabolites for biological activity is underscored. It has been reviewed that the most important alkaloids, such as Cephalotaxine-type alkaloids, homoerythrina-type alkaloids, and homoharringtonine (HHT), are abundant in Cephalotaxus lanceolata, C. fortunei var. alpina, C. griffithii, and C. hainanensis. Cephalotaxus alkaloids, particularly homoharringtonine (HHT), have emerged as promising anticancer agents with a unique mechanism of action and key oncogenic pathways. This review critically evaluates the understudied mechanisms of Cephalotaxus alkaloids in solid tumors, their translational barriers, and innovative strategies to harness their full anticancer potential. Additionally, we examine the challenges associated with their chemical complexity, regulatory hurdles, and toxicity profiles, alongside strategies to enhance efficacy through combination therapies and advanced drug delivery systems. The review highlights ongoing clinical trials and future directions, including synthetic biology and personalized medicine. By bridging traditional knowledge with contemporary research, this work highlights the potential of Cephalotaxus alkaloids as versatile agents in precision oncology.