Montreal – Researchers from the University of Ottawa have identified a mechanism that allows abnormal cells to multiply as if they were healthy, which could constitute an important asset in the fight against cancer.
This mechanism could also explain why certain cancers end up developing resistance to chemotherapy drugs that are used to destroy them.
“The best way to cause cancer in a human being or to any organization is to have DNA damage,” said Professor Damien d’Amours, of the Faculty of Medicine at the University of Ottawa.
“So we wanted to understand how cells listen or do not listen to the mechanisms, the rules of the cell cycle, which essentially tell them how or when they should divide or not.”
Usually, he said, the cells “do not like to divide at all when they have DNA damage because it can cause biggest damage and then it can cause cancer”.
The cells whose DNA is damaged are therefore normally unable to divide due to the damage they present.
The love teacher and the upper cycle student Laurence Langlois-Lemay have now discovered how these cells manage to circumvent the control points of the cell cycle which would normally prevent their division.
“We have found a mutation in a (enzyme) called Polo and which, in fact, begins to no longer listen to its cell cycle as it should,” he explained. And this mutation allows cells to “cheat”. ”
The first rule of cell division, he added, is that a cell is only divided when it receives a signal indicating it to do so. The second rule is that a damaged cell should never be divided.
It is this second rule that the identified mutation allows abnormal cells to break.
The love teacher, who holds Canada’s research chair on the dynamics of the chromatic and the architecture of the genome, believes that the main discovery of the study is very relevant for the treatment of cancer, since a large number of chemotherapeutic agents work by targeting and damaging the DNA of the tumor.
“A large fraction of therapy that is used to treat cancer in patients is based on the concept that is damaged (…) of patient cancer cells,” he said. And we want the cells to stop dividing in response to these damage. But if the cells do not respond to the rule not to divide when they have damage to DNA, they will not respond to therapy. “
It is estimated that the resistance to treatments contributes to 90 % of the deaths linked to cancer.
In other words, said the love teacher, the cells are damaged to activate the cell cycle stop mechanism.
But if the cells adapt to their damaged DNA, they can continue to divide, which can lead to resistance to chemotherapy, “and this is the big challenge in the treatment of cancer all over the world at the moment,” he said.
“If we inhibit (Polo), this decision-making process is restored not to divide in the presence of DNA damage,” summed up the love teacher.
The next step would be to test certain enzymes inhibitors of the Polo family in mice to see if it is necessary to organize clinical trials, he concluded.
The conclusions of this study were published by the renowned scientific newspaper Proceedings of the National Academy of Sciences.
