Antiangiogenics in Malignant Granular Cell Tumors: Review of the Literature

SIMPLE SUMMARY: Granular cell tumor (GCT) constitutes an ultra-rare subtype of soft tissue sarcoma (STS) that can exhibit aggressive behavior and limited survival in the metastatic setting. For metastatic GCTs, the therapeutic options are limited, as this tumor is relatively chemo-resistant. This review synthetizes the growing evidence for the relevant pazopanib benefit in advanced GCTs, while describing some insights on the pathology and the biology of these tumors. The data collected in this review suggest that pazopanib is substantially active in advanced GCTs in terms of dimensional responses. Pazopanib should be considered as a preferable treatment option for patients diagnosed with advanced GCTs. ABSTRACT: Granular cell tumors (GCT) represent 0.5% of all soft tissue sarcomas (STS), and when metastatic, they exhibit aggressive behavior and determine limited survival. Metastatic GCTs are relatively chemo-resistant; however, there is growing evidence of the benefit of using pazopanib and other targeted therapies in this histology. This is a review of the role of pazopanib and other targeted therapies in the treatment of GCTs, along with some insights on pathology and molecular biology described in GCTs. From 256 articles found in our search, 10 case-report articles met the inclusion criteria. Pazopanib was the most employed systemic therapy. The median reported time on therapy with pazopanib was seven months. Eight out of ten patients (80%) experienced disease control with pazopanib, while four out of ten (40%) patients achieved an objective RECIST response. Molecular studies suggested that antitumoral effects of pazopanib in GCT might be due to a loss-of-function of ATP6AP1/2 genes which consequently enhance signaling through several molecular pathways, such as SFKs, STAT5a/b, and PDGFR-β. Other reported targeted therapies for malignant GCTs included pazopanib in combination with crizotinib, which showed disease control for four months in one patient, and a PI3K inhibitor which achieved disease control for nine months in another patient. Dasatinib and megestrol were ineffective in two other different patients. Pazopanib has been demonstrated to be active in advanced GCTs and may be considered as a preferable treatment option.