Targeting aggressive osteosarcoma with a peptidase-enhanced cytotoxic melphalan flufenamide.

ABSTRACT:

Background

Low survival rates in metastatic high-grade osteosarcoma (HGOS) have remained stagnant for the last three decades. This study aims to investigate the role of aminopeptidase N (ANPEP) in HGOS progression and its targeting with a novel lipophilic peptidase-enhanced cytotoxic compound melphalan flufenamide (melflufen) in HGOS.

Methods

Meta-analysis of publicly available gene expression datasets was performed to determine the impact of ANPEP gene expression on metastasis-free survival of HGOS patients. The efficacy of standard-of-care anti-neoplastic drugs and a lipophilic peptidase-enhanced cytotoxic conjugate melflufen was investigated in patient-derived HGOS ex vivo models and cell lines. The kinetics of apoptosis and necrosis induced by melflufen and

SUBMITTER: Byrgazov K 

PROVIDER: S-EPMC7391428 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature