The Proteasome Inhibitor Ixazomib Inhibits the Formation and Growth of Pulmonary and Abdominal Osteosarcoma Metastases in Mice.

ABSTRACT: Osteosarcoma is the most common form of primary bone cancer. Over 20% of osteosarcoma patients present with pulmonary metastases at diagnosis, and nearly 70% of these patients fail to respond to treatment. Previous work revealed that human and canine osteosarcoma cell lines are extremely sensitive to the therapeutic proteasome inhibitor bortezomib in vitro. However, bortezomib has proven disappointingly ineffective against solid tumors including sarcomas in animal experiments and clinical trials. Poor tumor penetration has been speculated to account for the inconsistency between in vitro and in vivo responses of solid tumors to bortezomib. Here we show that the second-generation proteasome inhibitor ixazomib, which reportedly has enhanced solid tumor penetration compared to bortezomib, is

SUBMITTER: Harris MA 

PROVIDER: S-EPMC7281181 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature