Early study results indicate the potential for a new class of inhibitory compounds to enhance the effect of anti-tumor drugs in melanoma treatment. What the future may hold.
Blocking the activity of an enzyme called acid ceramidase makes human melanoma cells more sensitive to chemotherapeutic agents, according to a new study.1
Dr. Piomelli“Acid ceramidase controls the levels of two important messengers in cells, ceramide and sphingosine. These substances have opposing effects on cell fate: ceramide promotes cell death (apoptosis), whereas, sphingosine encourages survival and cell replication,” the study’s senior author Daniele Piomelli, Ph.D., M.D. (hon.), professor, departments of anatomy and neurobiology, and neurosciences chair, University of California Irvine, tells Dermatology Times. “When acid ceramidase is inhibited, ceramide levels increase and melanoma cells are ‘pushed’ toward apoptosis.”
Dr. Piomelli and colleagues found acid ceramidase is highly activated In skin biopsies of stage 2 melanomas. They report on the success of a class of molecules, which Dr. Piomelli helped to create, that inhibit acid ceramidase. In essence, the compounds act like multipliers that boost the deadly effects of conventional anti-tumor agents, according to a University of California, Irvine, press release.
Healthy tissue surrounding melanoma treated with the new compounds destroys the compounds, preventing the compounds’ spread to other organs or tissue.
“… a relevant aspect of our study is that we have discovered several small-molecule inhibitors for acid ceramidase, which could be eventually moved to the clinic,” Dr. Piomelli says. “It is a basic study, however, so the path to the patients is still long.”
1 Realini N, Palese F, Pizzirani D, et al. Acid Ceramidase in Melanoma: EXPRESSION, LOCALIZATION, AND EFFECTS OF PHARMACOLOGICAL INHIBITION. J Biol Chem. 2016;291(5):2422-34.