Pilot Study Explores Potential Therapeutic Target for Merkel Cell Carcinoma
Posted: Tuesday, December 17, 2019
In a pilot study, Merkel cell carcinoma has been found to often—but not always—be positive for Merkel cell polyomavirus large T-antigen expression, exhibiting predominant alternative tyrosine kinase A receptor (TrkA) III splicing, with evidence of intracellular TrkAIII activation. Published in the Journal of Experimental & Clinical Cancer Research, these findings indicate the possibility of a novel Merkel cell polyomavirus oncogenic mechanism and “a potential therapeutic target,” according to Andrew Reay Mackay, PhD, of the University of L’Aquila, Italy.
SV40 large T-antigen, an analog of Merkel cell polyomavirus large T-antigen, can promote the alternative TrkAIII splicing, noted the researchers. In their work, Dr. Mackay and colleagues found that 17 of the 18 Merkel cell carcinomas they studied were positive for Merkel cell polyomavirus large T-antigen expression, whereas 1 of the 18 tumors was Merkel cell polyomavirus large T-antigen–negative.
That last one, along with all the basal cell carcinoma (n = 3), squamous cell carcinoma (n = 3), and normal skin tissue (n = 2) samples studied, “exhibited exclusive fully-spliced TrkA mRNA expression, associated with variable immunoreactivity for nonphosphorylated but not phosphorylated TrkA.” Therefore, the team concluded, “TrkAIII splicing [could be] a novel potential oncogenic mechanism and therapeutic target in Merkel cell polyomavirus–positive Merkel cell carcinoma.”
Disclosure: The study authors reported no conflicts of interest.