Abstract
Triptolide, a compound isolated from a Chinese medicinal herb, possesses potent antitumor, immunosuppressive, and anti-inflammatory properties, but is clinically limited due to its poor solubility, bioavailability, and toxicity. Recently, Minnelide, a water-soluble prodrug of triptolide, was shown to have potent antitumor activity in various preclinical cancer models. Minnelide is currently in Phase II clinical trials for treatment of advanced pancreatic cancer, which has fueled increased interest in this promising agent. Here, we review the recent advances in the biological activity of triptolide and its analogs, their mechanisms of actions, and their clinical developments. A special emphasis is given to proteins and pathways within the tumor and stromal compartments that are targeted by triptolide and its analogs as well as the ongoing clinical trials.
Triptolide exhibits cytotoxicity toward both tumor cells and cancer-associated fibroblasts, and modulates immune microenvironment.
Triptolide induces cell death pathways, inhibits inflammation, reduces metastasis, and attenuates extracellular matrix protein production by cancer-associated fibroblasts.
Minnelide is a water-soluble prodrug of triptolide that shows potent in vitro and in vivo antitumor activity in a number of tumor types.
In a Phase I clinical trial with Minnelide, partial responses by RECIST (Response evaluation criteria in solid tumors) criteria were noted in patients with gastric and pancreatic cancer.
