TH1579, MTH1 inhibitor, delays tumour growth and inhibits metastases development in osteosarcoma model.

ABSTRACT:

Background

Osteosarcoma (OS) is the most common primary malignant bone tumour. Unfortunately, no new treatments are approved and over the last 30 years the survival rate remains only 30% at 5 years for poor responders justifying an urgent need of new therapies. The Mutt homolog 1 (MTH1) enzyme prevents incorporation of oxidized nucleotides into DNA and recently developed MTH1 inhibitors may offer therapeutic potential as MTH1 is overexpressed in various cancers.

Methods

The aim of this study was to evaluate the therapeutic benefits of targeting MTH1 with two chemical inhibitors, TH588 and TH1579 on human osteosarcoma cells. Preclinical efficacy of TH1579 was assessed in human osteosarcoma xenograft model on tumour growth and development of pulmonary metastases.

Findings</

SUBMITTER: Moukengue B 

PROVIDER: S-EPMC7063190 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature