Lucia’s legacy: the samples of his unusual tumor illuminate the resistances of this most cancers to remedies | Health and properly -being | EUROtoday

Lucía García was simply eight years previous when she was recognized with an odd mind tumor, very aggressive and incurable. It was an intrinsic diffuse glioma of the mind trunk (DIPG), a really uncommon most cancers – you may diagnose about twenty circumstances yearly in Spain – however able to making enjoyable of the immune system and escaping all of the remedies accessible to attempt to neutralize it. The woman died a 12 months after analysis, however left a legacy that may lay the foundations to assist flip the prognosis of a devastating illness: the samples of her tumor, donated by her kin, have allowed science to review the aggressiveness of this most cancers and likewise examine potential therapeutic targets to destroy it.

“The samples of the Lucia tumor have served a lot. Clinical trials have been justified using this tumor,” says Ángel Montero, head of the pediatric most cancers remedy group of the Sant Joan de Déu Research Institute in Barcelona. Precisely, this researcher has resorted to samples of the woman’s tumor and different sufferers to disclose the Dipg’s methods to make enjoyable of the immune system. In a current article printed within the journal Neuro-Oncology Advancesthe researchers of the Sant Joan de Déu have found that this tumor reinforces the blood vessels of their environment to stop any remedy and likewise secret proteins that camouflage it from the immune system.

Lucia was eight years previous when unusual complications started. They had been nonspecific, however persistent. Increasingly frequent. The medical doctors hypothesized that it may very well be one thing of the view, with out extra. But sooner or later, his dad and mom observed that he was additionally starting to be checked out his tongue and considered one of his eyes made unusual actions, and took her to the Emergency. A magnetic resonance revealed actuality and the worst of the forecasts: a mind tumor was inflicting all that.

The little woman entered that very same day on the Sant Joan de Déu hospital in Barcelona to begin the remedy, however the medical doctors had been frank with the household from the primary second, remembers Alfonso García, Father of Lucia: “They explained the disease and also a little the sequence of what was going to happen. And they nailed it.” There aren’t any therapeutic remedies and life expectancy after analysis is lower than two years.

Andrés Morales, Assistance Director of Pediatric Cancer Center of Sant Joan de Déu, who a analysis of Dipg is “one of those few situations” by which the medical crew sits with the household and from the primary second they clarify that there isn’t any therapeutic remedy. “When we verify that it is a high -risk DIPG, we know that in nine out of 10 cases, the patient will die in the first two years. And they die losing neurological faculties. Mortality is almost universal and, in addition, the family sees the patient deteriorates. It is very hard,” says Morales.

It has spent greater than a decade of that first time Lucia and her household crossed the doorways of Sant Joan de Déu, however Montero nonetheless has a snapped reminiscence of the woman, when she visited her laboratory, of the hopes deposited in a medical trial by which the little woman participated – he isn’t a health care provider, however he was current after they examined along with her an anti -control vaccine. The youngster was additionally one of many first sufferers who underwent a biopsy of the mind trunk within the hospital, remembers: “That of its tumor was our fourth biopsy. And it was very important because we could have that tumor, immortalize it in the laboratory, amplify it, study it and use it for many studies and to share it with dozens of international laboratories. This tumor is, approximately, in approximately 40 or 50 laboratories World, ”says Montero.

Lucia couldn’t see him, however because of the samples of his tumor – taken within the analysis, but additionally when he died – science has been giving passings ahead to know this unusual most cancers. Montero explains, for instance, that, when having tumor tissue samples of the start and the top of the method, the distinction between an unrelated tumor and the way these malignant cells advanced over time and after receiving varied remedies had been seen and after receiving varied remedies – the woman underwent cheim and radiotherapy, along with the experimental antitumor vaccine. “The main finding is that almost nothing changes: the initial tumors are very empty of immune cells and the final tumors persist empty of immune cells. There has nothing happened. What is the reason? We are not able to reach those tumors with any treatment. And there is the key,” says the scientist.

Lucia’s tumor is roughly 40 or 50 laboratories world wide “

Ángel Montero, scientist at the Sant Joan de Déu Research Institute in Barcelona

Along with the donation of another thirty families, the samples of the brain tissue of the child have also served Montero and their equipment to deepen even more in the behavior of this tumor and unravel why these malignant cells do not respond to any treatment.

From the analysis of brain tissue samples, cerebrospinal fluid and blood of patients with dipg and in vitro experiments with human cells and animal models, the team of scientists of Sant Joan de Déu revealed that tumor cells pervert everything that is around them. “The importance of these biopsy cells is that they can grow in the laboratory. What we have shown is that if we later put them in contact with other cells in the brain, which are in normal cell theory, such as macrophages [un tipo de células del sistema inmune]we see that all that touches that tumor is malignant, becomes protumoral, ”explains Montero.

Researchers have discovered that tumor cells secrete two proteins that change the surroundings around them to escape the immune system. “The secret tumor some substances to its microenvironment that makes macrophages change into protumoral. That is, out of the blue these macrophages have no idea something and in reality inactivate the lymphocytes that may attain there,” he says. In addition, these substances cause the blood vessels to be more sealed, that they are impenetrable: “If already in our brain, the blood vessels are especially well sealed so that it does not get intoxicated with anything, in the presence of the tumor, those blood vessels are even more isolated: they are better closed so that they do not between chemotherapy and secrete proteins that inactivate proteins that inactivate To lymphocytes. That is, even worse, ”laments the scientist.

Possible therapeutic targets

According to this investigation, the tumor is entrenched behind a wall of very robust molecular mechanisms. But Montero, although aware of the complexity of this disease, is optimistic: “We have two possible therapeutic targets to be able to attack more. We now know that those blood vessels and also pericitos [células que se encuentran en la pared de los vasos] They secrete a protein called B7H3. And in the scientific market there are antib7h3 therapies. That is, now you know the enemy and you know what can attack him. So, on the one hand, I believe that antib7h3 therapy, considered immunotherapy, has a lot of future and there are researchers in Seattle who are already investigating it. On the other hand, the blood brain barrier is more intact. Therefore, we have to develop drugs that are chemically modified to be able to transfer it, ”reflects the scientist.

For Morales, all these findings “are doorways that open and must discover.” But it measures their expectations. “There is a niche between analysis and clinic. It is within the translation to the clinic the place we discover the problem. It is a particularly complicated course of. Although we all know the biology of the tumor higher, the remedy has not modified considerably in these years. After virtually 300 medical trials, the survival curve has been moved little or no. Although now evidently immunotherapy can work in a subgroup of sufferers,” he says.

Alfonso García and Noelia Gómez, parents of little Lucia, keep all hopes in her daughter’s legacy. “Given this illness, as a father, you might be helpless. You can not do something. Absolutely nothing. This, at the least, is one thing. And you assume that if it has not served us in order to not lose our daughter, at the least, to serve different households sooner or later,” assumes Garcia. “Perhaps there’s a lot to discover a treatment for this illness, however from an investigation will be advantages for a lot of different ailments and that’s very invaluable to me,” adds the mother.

That first visit of Lucía and his family to the Laboratory of Montero left a scientific footprint that has not yet written its end. The samples of the girl’s tumor continue to travel through the laboratories of half the world, but also the girl’s brother, Seventhat he was 10 years old, he discovered during the child’s disease, “a world, the scientist, who didn’t know that there was,” the dad and mom say. And one thing nest there, as a result of at present the younger man is finding out biotechnology on the college and has simply finished a analysis keep, exactly, with Montero, in the identical laboratory {that a} decade in the past he first visited his sister’s hand.