Biomarkers and therapeutic targets in giant cell tumor of bone: A comprehensive review

Abstract

Giant cell tumor of bone (GCTB) is an intermediate locally aggressive osteolytic tumor with low metastatic potential and a high recurrence rate. It comprises two main types of cells—neoplastic mononuclear stromal cells and osteoclast-like giant cells—which are responsible for the resorption of bone. In addition to surgery, which is the primary treatment of choice, adjuvant therapy is used to lower the risk of recurrence. However, denosumab, the standard adjuvant treatment currently used, only targets osteoclast-like giant cells and does not affect neoplastic stromal cells. Since some GCTBs are inoperable, or even after surgery, there can be residual tumor cells at the site of the tumor, novel therapies, especially those that target neoplastic stromal cells, are needed. Both cell types in GCTB show altered expression of various specific genes and molecules, and these deregulated molecular profiles could serve as biomarkers and targets for targeted therapy. Herein, we summarize the potential biomarkers for both cell types in GCTB and therapeutic agents targeting these molecules with the hope of finding a therapy with improved outcomes and a lower risk of recurrence.