Pexidartinib and CSF1R Inhibitors as Treatment for Tenosynovial Giant Cell Tumors

Abstract

Tenosynovial giant cell tumor (TGCT)—previously referred to as giant cell tumor of the tendon sheath or pigmented villonodular synovitis—is a largely benign, rare, proliferative lesion arising from the synovial lining of joints, bursae, and tendon sheaths. TGCT has been classified into two clinically distinct yet genetically identical localized TGCT (TGCT-L): those that are typically cured with surgery alone; or diffuse types (TGCT-D), which are much more difficult to manage. A translocation involving the short arm of chromosome 1p11-13, with resultant hyperexpression of macrophage colony-stimulating factor 1 (CSF1), has since been shown to contribute, in large part, to the development of TGCT. Excessive resultant CSF1 secretion attracts monocytes and macrophages due to their expression of the CSF1 receptor (CSF1R). CSF1R inhibitors have been used with promise to improve patient outcomes in TGCT-D. Their role is increasing but is still largely undefined.