Epigenetic plasticity and resistance mechanisms

Study of the dynamic of epigenetic alteration acquisition during tumorogenesis

Céline Vallot

Background: Patient derived xenografts (PDX) models were developed at Institut Curie for chemotherapy-resistant triple negative breast cancers and for Tamoxifen-resistant ER+ breast cancers (cancers with estrogen receptors). Furthermore it has been shown that ER+ resistant tumors are characterized by a profound modification of their gene expression profile.

Hypothesis: Knowing that estrogen receptors regulate the transcription of certain genes by interacting directly at the DNA level and in endocrine resistant tumors the expression of these genes indicates that the transcriptional activity of estrogen receptors is deficient despite their presence it’s possible that epigenetic modifications are responsible for this deregulation.

An integrated study of genomic, epigenomic and transcriptomic characteristics during treatment could clarify the resistance mechanism and enable the development of new therapeutic approaches.

Objective: carry out an integrated clonal analysis of epi-transcriptomic changes before and during chemotherapy or targeted treatments.

Find out more about the research of the DEpiC team by listening the Céline Vallot’s interview (in French) with France Culture (15/02/2017)