A research team from the CNRS at the Paris Michel-Ange Delegation has determined that the introduction of epigenetic treatments could increase the success rate of chemotherapy.
Chemotherapies are effective in some patients; however, tumour cells develop a tolerance to these treatments. This means that the cells can learn and adapt to how chemotherapy treatments work so they can survive and essentially avoid being destroyed. Thus, researchers investigated how this can be avoided, and determined that the answer lies within the epigenetic mechanisms that regulate gene expression. This means that epigenetic treatments can aid in preventing cells from essentially re-writing themselves to avoid chemotherapy.
This study was published in Nature Genetics in April 2022.
How would epigenetic treatments work?
The study of epigenetics investigated how genes will be used or not used by a cell. The epigenome of a cell represents the set of chemical modifications of the DNA or associated proteins that will determine the expression of the genes and the cell’s identity.
This information, which is central from the development of the embryo onwards, leads to changes in how our genes are expressed without impacting their sequence. By modifying its epigenome, the cell can adapt quickly to its environment. Genetics and epigenetics work together to enable cells to perform their function – scientists intend to consider these mechanisms in the development of epigenetic treatments.
How was this developed?
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), analysed cell by cell in order to determine the epigenetic variations acquired by tumour cells during chemotherapy treatment.
In collaboration with the team of Léila Périé, a CNRS researcher at the Physico-chimie Curie (CNRS/Institut Curie/Sorbonne Université), the scientists identified the genes whose expression allowed cells to tolerate treatment, as well as the epigenomic modifications that regulated them.
Scientists have discovered that epigenomic marks ‘lock’ the expression of these genes in the absence of treatment, and that this lock jumps under chemotherapy in rare cells, allowing those cells to avoid being destroyed.
However, if this lock is prevented from jumping, all cancer cells will remain sensitive to treatment. Scientists have demonstrated this through epigenetic treatment, utilising chemical compounds called epi-drugs on animal models of breast cancer that inhibit the removal of epigenetic marks. While this experiment was successful, the molecules still need to be adapted for human use.
When will this treatment be applied?
Scientists have noted that these results clearly demonstrate the epigenome’s involvement in resistance to cancer treatment. Therefore, researchers are now actively seeking how to apply this concept to humans from a therapeutic perspective. If future clinical trials are convincing, scientists intend for these epigenetic treatments to be utilised in conjunction with chemotherapies to prolong their effectiveness in patients.
