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Chromatin Regulators as a Guide for Cancer Treatment Choice

Zachary A Gurard-Levin1, Laurence O W Wilson2, Vera Pancaldi3

  • 1Institut Curie, PSL Research University, CNRS, UMR3664, Equipe Labellisée Ligue contre le Cancer, Paris, France. Sorbonne Universités, UPMC Universite Paris 06, CNRS, UMR3664, Paris, France. zachary.gurard-levin@curie.fr genevieve.almouzni@curie.fr.

Molecular Cancer Therapeutics
|May 20, 2016
PubMed

Insights

Predicting chemotherapy response is challenging. Chromatin regulators, like SWI/SNF components, can predict docetaxel response in breast cancer and may serve as therapeutic targets to overcome drug resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Predicting patient response to chemotherapy is a significant challenge in cancer treatment.
  • Chemotherapeutic efficacy is influenced by chromatin structure, and its alterations can lead to drug resistance.

Purpose of the Study:

  • To investigate the role of chromatin regulators in predicting patient response to docetaxel.
  • To identify specific chromatin regulators that can serve as biomarkers for docetaxel efficacy and as potential therapeutic targets.

Main Methods:

  • Analysis of Affymetrix and NanoString gene expression data from breast cancer patient-derived xenograft models and patient samples treated with docetaxel.
  • Utilized Random Forest classification to identify predictive gene panels.
  • Explored SWI/SNF component expression in the NCI-60 dataset and performed functional studies in a model cell line.

Main Results:

  • Specific panels of chromatin regulators, including SWI/SNF components, effectively distinguished between docetaxel high-responders and poor-responders.
  • SWI/SNF component expression inversely correlated with docetaxel sensitivity across multiple datasets.
  • Loss of the SWI/SNF subunit BRG1 (SMARCA4) enhanced docetaxel sensitivity in a model cell line.

Conclusions:

  • Chromatin regulators are promising biomarkers for predicting drug response to docetaxel.
  • Targeting chromatin regulators, particularly SWI/SNF components, may offer a strategy to sensitize patients to docetaxel and overcome therapeutic resistance.

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