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The Evolution of Anticancer Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
In recent years there has also been a resurgence of interest in ethnopharmacology (also known as ethnopharmacy or ethnobotany), the study of plant materials or other natural products that are used by local communities as a traditional cure for a particular disease. The assumption is that these materials may contain an active constituent that can be identified, purified, and obtained in large amounts (by extraction or synthesis) for further studies. One recent example of the success of this approach was the identification of a novel agent now used for the treatment of proliferative skin disorders, including nonmelanoma skin cancers. Researchers at the University of Birmingham (UK) and the company Peplin Ltd (Brisbane, Australia) discovered a new agent (initially known as PEP005 or 3-Angelate) in the sap of the weed Euphorbia peplus (also known as petty spurge or milk weed) which had a history of community use for the “folklore” treatment of corns, warts, and other skin lesions such as skin cancer. The researchers isolated ingenol as the active agent, and showed that it was 100 fold more cytotoxic toward certain tumor cells in vitro than healthy cells. Furthermore, evidence was obtained that it may work by activating the protein kinase C pathway, thus inducing the interleukin decoy receptors IL1R2 and IL13RA2 and triggering apoptosis. In 2004, two INDs were filed with the FDA for the clinical development of ingenol mebutate (PicatoTM) for solar keratoses and basal cell carcinoma. In 2009, Peplin Ltd was acquired by the pharmaceutical company Leo Pharma which specializes in dermatological products, and FDA approval for the topical treatment of actinic keratosis was obtained in 2012. Given this example of successful drug discovery and development, it is possible that more novel anticancer agent leads may be derived from natural product sources in the future.
Safety of topical interventions for the treatment of actinic keratosis
Published in Expert Opinion on Drug Safety, 2021
Elias A. T. Koch, Anja Wessely, Theresa Steeb, Carola Berking, Markus V. Heppt
IM is a macrocyclic diterpene ester extracted from the natural plant Euphorbia peplus. The exact mechanism of action of IM is not yet fully understood. A dual effect is assumed: On one hand, through its acute cytotoxic effect caused by loss of the mitochondrial membrane potential, IM leads to mitochondrial swelling and membrane depolarization and subsequently to rapid lesion necrosis. On the other hand, IM leads to an inflammatory response with infiltration of neutrophils leading to cell death through activation and release of reactive oxygen species [83,84].
Cancer prevention and treatment using combination therapy with natural compounds
Published in Expert Review of Clinical Pharmacology, 2020
The plant Euphorbia peplus (Euphorbiaceae) has been used as a home remedy for the treatment of various skin conditions, and clinical studies identified the active agent as ingenol-3-angelate. Its efficacy is thought to be through the activation of protein kinase C [77]. Several favorable clinical trials led to the approval by the FDA of the agent in 2012 for the topical treatment of actinic keratosis, a precancerous lesion of the skin [78].
Effect of topical dermatologic medications in humans on household pets
Published in Baylor University Medical Center Proceedings, 2020
Usman Asad, David Boothe, Michelle Tarbox
Accidental ingestion of topical imiquimod by mice has resulted in cutaneous inflammation via type I interferons.7 Ingestion of fodder contaminated with Euphorbia peplus, the source for ingenol mebutate, has led to severe systemic complications in lactating goats.8 Further studies may help to illustrate whether these effects can manifest in dogs, cats, or other common household pets.