New allies for chemotherapy? –ScienceDaily


If genetics is interested in the sequencing of genes, epigenetics studies how genes will be used, or not, by a cell. The epigenome of a cell represents all the chemical modifications of DNA or associated proteins that will determine the expression of genes and therefore the identity of the cell. This information, central from the development of the embryo, induces modifications in the expression of our genes without affecting their sequence. By modifying its epigenome, the cell can quickly adapt to its environment. Genetics and epigenetics work together to enable cells to perform their function.

A research team1 directed by Céline Vallot, CNRS research director within the Dynamics of Genetic Information Laboratory: Fundamental Bases and Cancer (CNRS/Institut Curie/Sorbonne University), and the Translational Research Department of the Institut Curie (CNRS/Institut Curie /Sorbonne University), analyzed cell by cell the epigenetic variations acquired by tumor cells during chemotherapy treatment. In collaboration with the team of Léila Périé, CNRS researcher at Curie Physico-Chemistry (CNRS/Institut Curie/Sorbonne University), the scientists identified the genes whose expression allowed cells to tolerate2 treatment, as well as the epigenomic modifications that regulate them. Scientists have discovered that epigenomic marks “lock” the expression of these genes in the absence of treatment, and that this lock is broken under chemotherapy in rare cells. If this lock is prevented from jumping, all cancer cells remain susceptible to treatment. Scientists have demonstrated this using chemical compounds called epi-drugs3 in animal models of breast cancer that inhibit the elimination of epigenetic marks. These molecules have yet to be adapted for human use.

These results clearly demonstrate the involvement of the epigenome in resistance to cancer treatments. Scientists are now actively researching how to apply this concept to humans from a therapeutic perspective. If future clinical trials are conclusive, scientists imagine that these epi-treatments could be used in combination with chemotherapy to prolong their effectiveness in patients.

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Journal reference:

  1. Justine Marsolier, Pacôme Prompsy, Adeline Durand, Anne-Marie Lyne, Camille Landragin, Amandine Trouchet, Sabrina Tenreira Bento, Almut Eisele, Sophie Foulon, Léa Baudre, Kevin Grosselin, Mylène Bohec, Sylvain Baulande, Ahmed Dahmani, Laura Sourd, Eric Letouzé , Anne-Vincent Salomon, Elisabetta Marangoni, Leïla Perié, Céline Vallot. H3K27me3 conditions chemotolerance in triple negative breast cancer. Natural genetics, 2022; 54(4):459 DOI:10.1038/s41588-022-01047-6

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