Genome Medicine (Sep 2020)

Personalized cancer therapy prioritization based on driver alteration co-occurrence patterns

  • Lidia Mateo,
  • Miquel Duran-Frigola,
  • Albert Gris-Oliver,
  • Marta Palafox,
  • Maurizio Scaltriti,
  • Pedram Razavi,
  • Sarat Chandarlapaty,
  • Joaquin Arribas,
  • Meritxell Bellet,
  • Violeta Serra,
  • Patrick Aloy

DOI
https://doi.org/10.1186/s13073-020-00774-x
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 23

Abstract

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Abstract Identification of actionable genomic vulnerabilities is key to precision oncology. Utilizing a large-scale drug screening in patient-derived xenografts, we uncover driver gene alteration connections, derive driver co-occurrence (DCO) networks, and relate these to drug sensitivity. Our collection of 53 drug-response predictors attains an average balanced accuracy of 58% in a cross-validation setting, rising to 66% for a subset of high-confidence predictions. We experimentally validated 12 out of 14 predictions in mice and adapted our strategy to obtain drug-response models from patients’ progression-free survival data. Our strategy reveals links between oncogenic alterations, increasing the clinical impact of genomic profiling.

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