Scientists are finding a way to better comprehend the mechanisms behind the origin and spread of melanoma tumors and have discovered a possible place for a 10-year-old antibacterial agent in treating these aggressive forms of cancer. With information reported in the journal Cell Death and Differentiation, the study demonstrates that a specific enzyme, guanosine monophosphate synthase (GMPS), drives melanoma growth and proposes a new pharmaceutical plan for targeting that protein.
Following up on their previous work that displayed the prominent role played by deregulation of guanylate metabolism in melanoma growth, a study led by Mikhali Nikiforov, PhD, of Roswell park Cancer Institute (RCPI) researched the role of GMPS, a crucial enzyme in guanylate metabolism, found in melanoma development and metastasis. Guanylates, as the precursors to one of the four bases that make up RNA, play a crucial part in cells. The authors evaluated the effects of GMPS reduction and discovered the possibility of targeting GMPS by angustmycin A, also known as decoyinine. While this active ingredient was found in the early 1950’s as a possible antibiotic, it has not been experimentally tested as a catalyst for anti tumor nor tested at all in clinical settings.
Dr. Nikiforov and colleagues give examples in this latest research that GMPS levels are higher in human metastatic melanoma specimens and that pharmaceutical inhibition of GMPS by angustmycin A has the possibility to be efficient as a targeted anti- melanoma therapy for tumors hosting either of the two most typical mutations BRAFV600E and NRASQ61R.
“These are early, preclinical findings, but they open up the exciting prospect of possibly treating melanoma with an inexpensive and well-tolerated agent,” stated Dr. Nikiforov. “And because we have previously shown that guanylate pools can influence the invasion of cell lines derived from other types of cancer as well, we are also excited about the possibility of uncovering widespread mechanisms and targets that can be common to other kinds of tumors.”