Bioinformatic scripts used to generate the figures and analyses in:

Medina-Jover F, Figueras A, Gendrau-Sanclemente N, et al. Pujana MA, Perales JC, Viñals F. A rise in double-strand breaks sensitizes tumors to oxidative metabolism inhibitors. Biomedicine & Pharmacotherapy. 2026;197:119184. DOI: 10.1016/j.biopha.2026.119184

Summary

Double-strand breaks (DSBs) accumulate in tumor DNA due to homologous recombination (HR) deficiency (e.g., BRCA mutations) or antitumor treatment. This study shows that DSB accumulation, regardless of origin, triggers a shift toward oxidative metabolism (OXPHOS) via downregulation of HIF-1α, which reduces PDHK1 expression and activates the pyruvate dehydrogenase complex. This metabolic switch is a therapeutically actionable vulnerability: combining OXPHOS inhibitors with DSB-inducing chemotherapy produces strong synergy in vitro and in vivo, independent of HR status.

Contents

• data/ — input datasets used for the analyses (TCGA, GDSC, CCLE-derived signature scores, etc.)
• scripts/ — analysis code, including ssGSEA/signature scoring and correlation analyses
• results/ — output tables from the analyses
• figures/ — code and outputs for reproducing the manuscript figures

Methods reference

Signature scores (A-EJ, OXPHOS/KEGG, Mootha Voxphos, respiratory chain complex I, hypoxia, glycolysis, HIF-1α targets) were computed using single-sample GSEA (ssGSEA) via the GSVA R package (v1.43.1), applied to TCGA FPKM-UQ RNA-seq data. See the Methods section of the paper for full details on data sources (TCGA, GDSC, CCLE, ChIP-Atlas) and statistical methods.

Usage

# Example — update once script entry points are confirmed
source("scripts/[script_name].R")

Citation

If you use this code, please cite the publication above.