What if we made cancer an ally so we could overcome it? Confusing at first, one quickly perceives what Professor and Scientist Carmo Fonseca was willing to discover. Creating breast cancer in the laboratory and watching its birth, so you can study the early signs of the disease.



The challenge was launched by women from the EVITA Association who are at risk for breast cancer because they carry the genetic mutation of BRCA (mutations in genes that increase the chances of developing breast cancer). "This is a very active association and they called all Portuguese researchers and told us that they lived with a sword over their head with the possibility of having breast cancer," explained Carmo Fonseca. "The idea of to be able to perceive what is going on inside a woman's body and if there is a way to avoid or detect changes that indicate signs of the disease" was what motivated her to accept this cry for help. "I could not stay immune to this challenge, and thought about it for a long time, and with the skills we have in our Laboratory, that we could grasp this problem. So what came to me was that we have to watch the birth of cancer to find answers. All the research that has been done is on cancer that has already been formed, what has never been witnessed is the birth of breast cancer."

To recreate a cancer, we had to recreate the breast using women's skin with such genetic mutations, only then will the disease be induced, recreating an ageing process that will translate to time passing that will reflect life habits with risks: tobacco, alcoholic beverages, sun exposure, or sedentary lifestyle. "All cancers are formed due to DNA damage, depending on the type of lesions suffered, the cancer has its own pathway. Watching the birth of the cancer already within a BRCA mutation, means we're talking about a specific cancer."

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How do we induce external factors such as excessive sun exposure, smoking or alcohol consumption?

Carmo Fonseca: It is induced by creating lesions in the DNA. All these agents, which are carcinogenic, what they do is damage the DNA. We're going to use chemical means to produce the same effect.

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How do we measure the right proportion of these chemicals to know if we are inducing the disease?

Carmo Fonseca: It is measured by the number of lesions. It's like they're wounds, like we're going through a machine gun and our DNA is wounded every time it hits you. Then what happens is that we have a system that repairs, it's as if there are "surgeons" inside our cells that will repair the wounds and that system is called DNA repair and it happens inside the cell. The BRCA gene, which is mutated in these women, is one of the major "surgeons" in this "repair service," sometimes those who have a defective BRCA repair the damage less, becoming more exposed and vulnerable.

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What is the big advantage of this research, predicting how the disease appears or studying more treatment options?

Carmo Fonseca: As we watch the first phases, I am hopeful that we will learn more about how the disease appears and therefore help in the prevention and early diagnosis and not so much in the treatment, that won't be our focus.

But because we talk about ageing cells themselves and the time the whole process takes, there are also timings to be respected.

Carmo Fonseca: From a scientific perspective, it is very interesting for me because I have been talking to researchers who are dedicated to ageing and I have been talking to them about how I can accelerate the ageing process. Therefore, all the molecules that have been associated with ageing, I will use them to test the hypothesis that I can accelerate ageing of these laboratory cells. This will be an excellent proof of concept for scientists who want to reverse ageing. We will prove that those molecules are really important and if they are effective, that is going to be another very interesting aspect of the project.

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Optimised in several phases and because it is a pioneer project, one cannot predict the time it will take to get the first news or the first results. In a trial / error cycle, Carmo Fonseca and her young team of researchers know that success involves trying and perhaps often failing. And that happened when collecting these women's skin cells and reprogramming stem cells, that is, by reversing the cell to an embryonic state, the cells were lost. "In an experiment that took a month and everything seemed to be ready for differentiation into the mammary epithelial (cellular tissues), there was something that did not work."

Thus, returning to square one, forcing us to do the procedure differently, optimising the ingredients. But because experience is an ally of perseverance, already so entrenched in Carmo Fonseca, in a bad result there are also important lessons to take, "it is still possible to see if the ability to repair has been affected in these cells, because we are in the "DNA shots" phase, with the cells of women carrying the mutation and we will compare how quickly the wounds are repaired between normal cells with the cells of these women.

The experiment is already underway and with 200,000 euros of funding from the Foundation for Science and Technology (FCT). The team comprises a medical student, a master's degree student, and will soon have a postdoctoral degree student as well.

As for the drivers of the challenge, the women of the EVITA Association speak regularly with Carmo Fonseca and visit her to take a look at their cells' life and will certainly be the first to want to receive updates, wishing it will always be good news.

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Joana Sousa

Editorial Team