We are not helpless when it comes to cancer. Almost all animal species, including humans, have natural barriers against the uncontrolled proliferation of cells. To become cancerous, cells must therefore bypass these protective mechanisms. The best known of these, senescence, involves telomeres, a type of “cap” located at the end of our chromosomes. “They play a crucial role in the development of cancers. Normally, with each cell division, telomeres shorten. When they become too short, the cells stop dividing, die or turn into non-cancerous cells.”explains Miguel Godinho Ferreira, research director at IRCAN (Institute for Research on Cancer and Aging) in Nice.
To bypass this natural barrier, most cancers (around 90%) use an enzyme called telomerase, capable of lengthening their telomeres. “Proof of the need for telomerase for tumor development, mutations inducing the expression of this enzyme are now recognized as the most common genetic alteration in all cancers, continues the researcher, recognized worldwide for his work on these crucial mechanisms. In contrast, certain cancers, such as neuroblastoma, which lack telomere maintenance mechanisms, often have a better prognosis because they regress spontaneously or are easier to treat.”
Telomerase, essential in advanced stages
Although knowledge about these processes continues to accumulate, an important question remains: “We still do not know at what precise moment in the development of a tumor, telomere maintenance mechanisms become essential.”
To answer this question, Miguel Godinho Ferreira and his team studied the occurrence of melanomas (skin cancers) in zebrafish, a model widely used to explore the molecular pathways of cancer.
A new therapeutic route
“Our work has shown that melanomas, in their early stages, can develop without activating these mechanisms; tumors form and progress normally, even without telomerase. It is only at advanced stages, when telomeres reach a size Critically, telomerase becomes essential. Cancer cells must then reactivate this enzyme to continue dividing. If they fail to do so, tumor growth stops and the tumors may even regress or even disappear.
These discoveries open up new therapeutic avenues: it could be possible to target telomerase at the appropriate time or to strengthen the immune response. “In addition to their role in cancer growth, telomere maintenance mechanisms can also influence the response to immunotherapies [traitements qui stimulent le système immunitaire pour combattre le cancer, N.D.L.R.]. Some cancers activate telomerase very early, which makes them more resistant to immunotherapy.”
The discoveries of the team of scientists from Nice were published last December in the excellent journal Cell Reportsproof of their importance.
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