Sacituzumab govitecan inhibits bone metastases of TROP2-expressing cancers

Bone metastasis is a major cause of morbidity in patients with advanced cancers and remains largely incurable. Trophoblast cell surface antigen 2 (TROP2), which is highly expressed in various malignancies, represents a promising therapeutic target. Sacituzumab govitecan (SG), an antibody-drug conjugate (ADC) targeting TROP2 and carrying SN-38, has demonstrated clinical efficacy in treating several types of solid tumors. However, its effects on bone metastases remain unclear. In this study, we investigated the inhibitory effects of SG on bone metastases using preclinical models of breast and prostate cancer. In vitro, SG reduced the viability of bone-metastatic cancer cells in a dose-dependent manner. However, the effects did not clearly correlate with TROP2 expression levels and were comparable to those of irinotecan. In contrast, in vivo studies demonstrated markedly enhanced antitumor activity in TROP2-expressing tumors. SG almost completely suppressed mammary tumor growth and bone metastases of TROP2-overexpressing MDA-MB-231 breast cancer cells, whereas its effects on control cells were limited. Similarly, SG strongly inhibited subcutaneous tumor growth and bone metastases of TROP2^high PC-3 prostate cancer cells, but not TROP2^low cells. No severe toxicity was observed in treated mice. TROP2 expression was not consistently associated with malignant phenotypes in the models examined. These findings demonstrate the potent inhibitory effects of SG on bone metastases of TROP2-expressing cancers and provide preclinical evidence supporting the therapeutic potential of TROP2-targeted ADCs for metastatic bone disease.