Protein May Be Useful Target for Cancer Therapy
Deletion of fibroblast activation protein or drug inhibition linked to anti-tumor effect in mice
THURSDAY, Dec. 3 (HealthDay News) -- In several types of tumors, targeting the cell surface protease known as fibroblast activation protein (FAP) can inhibit tumor growth, according to research published in the Dec. 1 issue of the Journal of Clinical Investigation.
Angelica M. Santos, Ph.D., of the Wistar Institute in Philadelphia, and colleagues write that, in more than 90 percent of examined human epithelial cancers, tumor-associated fibroblasts and pericytes express FAP.
The authors found that in a mouse model of lung cancer, deletion of FAP was associated with decreased tumor burden. In mouse models of lung and colon cancer, the FAP inhibitor PT630 significantly inhibited tumor growth. In addition, they found that in lung tumors, inhibiting dipeptidyl peptidase IV -- which is related -- can also hinder tumor growth.
"In summary, this study provides proof of principle that targeting FAP can inhibit tumor growth in multiple tumor types, indirectly through effects on stromagenesis, vascularization, and ECM remodeling. Human epithelial-derived solid tumors are rich in FAP-expressing cells. Thus, in addition to establishing the mechanisms by which a specific stromal cell surface protease promotes tumorigenesis, these studies indicate that further exploring tumor stroma and, in particular, FAP as a potential therapeutic target in patients is warranted," the authors conclude.
A co-author reported past research support from Point Therapeutics, which provided materials for this study and employs another co-author.