Oral transforming growth factor‐beta receptor 1 inhibitor vactosertib promotes osteosarcoma regression by targeting tumor proliferation and enhancing anti‐tumor immunity
Year: 2024
Type: article
Abstract: Osteosarcoma (OS) is an aggressive malignant bone cancer, with refractory and metastatic disease remaining a significant challenge. Transforming growth factor-β1 (TGF-β) is a potent immune suppressive cytokine in OS and the TGF-β is increased in the sera of OS patients and this increase is associated with high-grade OS and lung metastases. Therefore, blocking TGF-β1 signaling may be a novel therapy for OS treatment. Here we show that blocking TGF-β1 signaling using TGF-βR1 inhibitor, Vactosertib, significantly inhibited OS proliferation in vitro and in vivo. Notably, Vactosertib inhibits c-Myc expression in the OS cells. Vactosertib increased immune effectors (IFNγ+CD8+ cells and NK cells) and inhibited immune suppressors (M2-like TAM, MDSC) in the OS tumor microenvironment. Our results suggest that inhibition of TGF-β1 signaling is an effective therapeutic strategy against OS through a multi-pronged approach that targets tumor intrinsic and extrinsic factors to achieve optimal immune-effector functions and maximal clinical response.
Source: 癌症：英文版
DOI: 10.1002/cac2.12589
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,800
Awards: Clinical Oncology Research Program (CORP), Medical Scientist Training Program, Mechanisms of TGF-β-induced resistance to proteasome inhibitors in multiplemyeloma, Characterizing a new antibody targeting growth-arrested breast cancer cells, Case Comprehensive Cancer Center Support Grant, Medical Scientist Training Program at Case Western Reserve University, c-Myc regulation by TGF-beta signaling as a therapeutic target in Osteosarcoma, Cancer Biology Training Grant
OpenAlex ID: W4400386895