MYC Inhibition By Omomyc Causes DNA Damage And Overcomes PARPi Resistance In Breast Cancer.

This study investigates the role of MYC dysregulation in DNA damage response (DDR) and PARP inhibitor (PARPi) resistance in breast cancer. Using Omomyc, a direct MYC inhibitor, we demonstrate that MYC inhibition shuts down DDR genes in triple-negative breast cancer (TNBC), causing DNA repair defects and inducing DNA damage that synergizes with PARPi treatment. Through patient-derived models and clinical samples from metastatic HR-altered breast cancer patients treated with PARPi, we identify MYC transcriptional activity as a predictive biomarker of PARPi resistance. Digital spatial profiling (DSP) analysis of pre-treatment tumor biopsies reveals that patients with progressive disease have significantly elevated MYC signatures compared to responders. These findings support the therapeutic strategy of combining MYC inhibition with PARPi in PARPi-resistant breast cancers where high MYC activity predicts poor response to therapy.

Type: Transcriptome Analysis
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

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Dataset ID	Description	Technology	Samples
EGAD50000001932	This dataset contains GeoMx digital spatial profiling (DSP) data from 12 FFPE pre-treatment biopsies of metastatic HR-altered breast cancer patients subsequently treated with PARP inhibitors (Olaparib or Talazoparib). Samples were collected from primary breast tumors (n=7) and metastatic sites including lymph nodes (n=2), bone (n=2), and brain (n=1). Tissue sections were stained for pan-cytokeratin (PANCK) to selectively profile tumor cells, with NGS-based transcriptome data generated for both PANCK+ and PANCK- regions. The dataset includes raw data files (176 fastq files) along with clinical annotations.	NextSeq 2000	13

Publications	Citations
MYC inhibition by Omomyc causes DNA damage and overcomes PARPi resistance in breast cancer. Giuntini F, González-Larreategui Í, Herencia-Ropero A, Casacuberta-Serra S, Zacarías-Fluck MF, Arnal M, Pedretti F, Martínez-Martín S, Thabussot H, Cano VC, Grueso J, Foradada L, Serrano E, López-Estévez S, Rodriguez O, Guzman M, Rodriguez-Hernandez A, Brasó-Maristany F, Llop-Guevara A, Balmaña J, Nonell L, Prat A, Serra V, Beaulieu ME, Whitfield JR, Massó-Vallés D, Soucek L. Cell Rep 44: 2025 116604	0

Publications

Citations

MYC inhibition by Omomyc causes DNA damage and overcomes PARPi resistance in breast cancer.
Giuntini F, González-Larreategui Í, Herencia-Ropero A, Casacuberta-Serra S, Zacarías-Fluck MF, Arnal M, Pedretti F, Martínez-Martín S, Thabussot H, Cano VC, Grueso J, Foradada L, Serrano E, López-Estévez S, Rodriguez O, Guzman M, Rodriguez-Hernandez A, Brasó-Maristany F, Llop-Guevara A, Balmaña J, Nonell L, Prat A, Serra V, Beaulieu ME, Whitfield JR, Massó-Vallés D, Soucek L. Cell Rep 44: 2025 116604