Computational Screening of Anti-Cancer Drugs Identifies a New BRCA Independent Gene Expression Signature to Predict Breast Cancer Sensitivity to Cisplatin - Centre de Recherche en Cancérologie de Marseille Accéder directement au contenu
Article Dans Une Revue Cancers Année : 2022

Computational Screening of Anti-Cancer Drugs Identifies a New BRCA Independent Gene Expression Signature to Predict Breast Cancer Sensitivity to Cisplatin

Jean Berthelet
  • Fonction : Auteur
Momeneh Foroutan
  • Fonction : Auteur
Dharmesh Bhuva
  • Fonction : Auteur
Holly Whitfield
Farrah El-Saafin
  • Fonction : Auteur
Joseph Cursons
  • Fonction : Auteur
Antonin Serrano
  • Fonction : Auteur
Michal Merdas
  • Fonction : Auteur
Elgene Lim
Emmanuelle Charafe-Jauffret
  • Fonction : Auteur
Matthias Ernst
  • Fonction : Auteur
Frédéric Hollande
Robin Anderson
Bhupinder Pal
  • Fonction : Auteur
Belinda Yeo
  • Fonction : Auteur
Melissa Davis
  • Fonction : Auteur
Delphine Merino

Résumé

The development of therapies that target specific disease subtypes has dramatically improved outcomes for patients with breast cancer. However, survival gains have not been uniform across patients, even within a given molecular subtype. Large collections of publicly available drug screening data matched with transcriptomic measurements have facilitated the development of computational models that predict response to therapy. Here, we generated a series of predictive gene signatures to estimate the sensitivity of breast cancer samples to 90 drugs, comprising FDA-approved drugs or compounds in early development. To achieve this, we used a cell line-based drug screen with matched transcriptomic data to derive in silico models that we validated in large independent datasets obtained from cell lines and patient-derived xenograft (PDX) models. Robust computational signatures were obtained for 28 drugs and used to predict drug efficacy in a set of PDX models. We found that our signature for cisplatin can be used to identify tumors that are likely to respond to this drug, even in absence of the BRCA-1 mutation routinely used to select patients for platinum-based therapies. This clinically relevant observation was confirmed in multiple PDXs. Our study foreshadows an effective delivery approach for precision medicine.
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Dates et versions

hal-03958429 , version 1 (21-06-2023)

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Jean Berthelet, Momeneh Foroutan, Dharmesh Bhuva, Holly Whitfield, Farrah El-Saafin, et al.. Computational Screening of Anti-Cancer Drugs Identifies a New BRCA Independent Gene Expression Signature to Predict Breast Cancer Sensitivity to Cisplatin. Cancers, 2022, 14 (10), pp.2404. ⟨10.3390/cancers14102404⟩. ⟨hal-03958429⟩

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