Researchers develop epigenetic methods for effective cancer treatments

If genetics is concerned with gene sequencing, epigenetics is concerned with how genes are employed (or not) by a cell. The epigenome of a cell is the collection of chemical alterations to DNA or related proteins that control gene expression and consequently the cell’s identity.

This input, which is crucial from the embryo’s development forward, causes changes in the expression of our genes without modifying their sequence. The cell can adjust quickly to its surroundings by altering its epigenome. To enable cells to accomplish their purpose, genetics and epigenetics operate together.

A research team led by Celine Vallot, CNRS Research Director in the Laboratoire Dynamique de l’information Génétique: Bases Fondamentales et Cancer (CNRS/Institut Curie/Sorbonne Université), and the Département de Recherche Translationnelle de l’Institut Curie (CNRS/Institut Curie/Sorbonne University), looked at the epigenetic changes that tumor cells obtained during chemotherapy treatment cell by cell.

In collaboration with the team of Léila Périé, a CNRS researcher at the Physico-chimie Curie (CNRS/Institut Curie/Sorbonne Université), the researchers identified the genes that enabled cells to survive therapy, as well as the epigenomic alterations that control their expression. Researchers showed that in the absence of treatment, epigenomic markers “lock” the expression of certain genes, and that this lock is broken by chemotherapy in rare cells.

All cancer cells stay responsive to treatment if this lock is kept from jumping. Researchers confirmed this by employing epi-drugs, which are chemical substances that prevent epigenetic marks from being removed, on animal models of breast cancer. These compounds must yet be modified for human usage.

These findings show that the epigenome has a role in cancer treatment resistance. Researchers are currently working hard to figure out how to apply this principle to humans in a therapeutic way. Scientists believe that if future clinical trials are successful, these epi-treatments could be used in combination with chemotherapies to extend their potency in patients.

Source:
Journal reference:

Marsolier, J., et al. (2022) H3K27me3 conditions chemotolerance in triple-negative breast cancer. Nature Genetics. doi.org/10.1038/s41588-022-01047-6.

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