Targeting serine/glycine metabolism improves radiotherapy response in non-small cell lung cancer.

ABSTRACT:

Background

Lung cancer is the most lethal cancer, and 85% of cases are classified as non-small cell lung cancer (NSCLC). Metabolic rewiring is a cancer hallmark that causes treatment resistance, and lacks insights into serine/glycine pathway adaptations upon radiotherapy.

Methods

We analyzed radiotherapy responses using mass-spectrometry-based metabolomics in NSCLC patient's plasma and cell lines. Efficacy of serine/glycine conversion inhibitor sertraline with radiotherapy was investigated by proliferation, clonogenic and spheroid assays, and in vivo using a serine/glycine dependent NSCLC mouse model by assessment of tumor growth, metabolite and cytokine levels, and immune signatures.

Results

Serine/glycine pathway metabolites were significantly consumed in response t

SUBMITTER: Sanchez-Castillo A 

PROVIDER: S-EPMC10876524 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature