The research involves two inhibitors of fibroblast activation protein (FAP), which has been implicated in human tumor growth. Talabostat (PT-100) and PT-630-- developed by Point Therapeutics (Boston, Mass.) suppressed tumor growth in mouse models, according to new data presented today at the American Association for Cancer Research 97th Annual Meeting in Washington, D.C., by Jonathan Cheng, M.D., Fox Chase Cancer Center.
FAP is a member of the DPP family, which are enzymes that appear to regulate several different physiological processes including tumor growth and immune responses.
Cheng's study demonstrated that both PT-100 and PT-630 inhibited FAP enzymatic activity and attenuated tumor growth in mice. PT-100 has been reported to upregulate the production of cytokines and chemokines leading to stimulation of the innate and adaptive immune system. In contrast, PT-630 inhibits FAP activity but is not known to induce cytokine and chemokine upregulation. Fox Chase scientists used mice that lack an adaptive immune system due the absence of T and B lymphocytes to control for talabostat's immunostimulatory activity and isolate the role of FAP in tumor growth. "The anti-tumor activity of both talabostat and PT-630 is intriguing because it suggests a mechanism of action involving tumor-targeted FAP inhibition that may be distinct from immune stimulation in tumor types where FAP is expressed clinically," said Cheng. "This may be a potentially novel way to treat cancer."
About fibroblast activation protein (FAP)
Fibroblast activation protein is a member of the dipeptidyl peptidase (DPP) family of serine proteases that is not present in most healthy tissues but is expressed on the tumor stroma of epithelial cancers, melanoma, and by certain sarcomas. It
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