Spanish science has once again demonstrated the great talent we have in our country and of which we should feel proud. One of the most recognized names is undoubtedly Mariano Barbacid, who joins his team has achieved something unprecedented until now: leave no trace of the pancreatic ductal adenocarcinomaone of those with the worst prognosis. But there are nuances to take into account.
A resistant cancer. If there is something that is feared in medicine, it is the diagnosis of a cancer that affects the pancreas due to its great mortality because it is difficult to diagnose it early and especially because of its resistance to treatments. Therefore, when the National Cancer Research Center (CNIO) publish in PNAS who has managed to eliminate these tumors in micethe scientific world turns its head.
The team led by Mariano Barbacid has achieved what is technically called a “complete and long-lasting regression.” Or in plain words: they have cured the mice. But before you throw the bells in the air, you have to read the fine print of biology: this is a preclinical milestone, not a ready-made therapy for humans.
A triple therapy. Until now, attacking pancreatic cancer was like trying to stop a car by cutting a single cable, since the tumor had alternative routes available to evade treatment and continue developing. But now Mariano Barbacid’s team has focused on cutting all possible routes.
To do this, they have created a therapy aimed at simultaneously attacking three critical points of the tumor. Technically, they have used three drugs to inhibit its growth pathway, such as KRASthe escape route in the EGFR protein and also the ‘shield’ it had by eliminating the STAT3 protein which is key for tumor resistance.
The result. By combining the three, they were able to eliminate tumors in mouse models, including PDX models, which are mice implanted with tumor tissue from human patients. The most surprising thing is the durability: more than 200 days without a trace of the disease after completing the treatment, and without apparent toxicity.
It won’t be ready for tomorrow. When this news emerges, the emotion is evident in different fields of science and also in society in general, since we are talking about a cancer that has destroyed many families. But the reality is that science does not move as fast as we would like and this treatment It still has a long way to go until it reaches the oncology units of hospitals. If everything goes well.
Your main barrier. There are three fundamental barriers that explain why a clinical trial could take around three years to start for this triple therapy. The main one is that of the three components that are used in this cocktail, only one, which is afatinibis approved and marketed. And this is a serious problem.
RMC-6236 It is the other drug that is currently in a clinical trial to test its safety and effectiveness. But the case of SD36, one of the most important drugs, is even more incipient since right now it is not approved by any regulatory agency. This reminds us that turning an experimental compound into a safe pill for humans takes time and a lot of regulatory bureaucracy.
The problem of toxicity. But beyond this, we must keep in mind that a mouse and a human have many differences in their organism. This makes what a mouse tolerates, a human sometimes cannot. In this way, the real effect on humans of this triple therapy and the toxicity it presents remains to be seen, although the good result in mice opens a door to hope and the need to continue betting on science and Spanish talent.
The shadow of resistance. Carmen Guerra, CNIO researcher and co-author of the study, has put her finger on the problem: have already identified mutations that confer resistance to this triple therapy. This means that even if it works in humans, it is likely not a definitive solution for all patients.
And pancreatic cancer in colloquial terms has a lot of bad milk This makes it truly heterogeneous, so even if a treatment works for one patient, it is not the same for others.
A Spanish milestone. Despite all these nuances that are necessary to come down to earth, what the CNIO team has achieved is extraordinary and reminds us how important it is to commit to science. made in Spain with greater financing. The fact that pancreatic cancer is a veritable graveyard of drugs that work in the laboratory and fail in the hospital gives a lot of weight to achieving a complete reversal in animal models.
Patience. What are we waiting for now? You have to be patient. Science advances step by step, with a large amount of bureaucracy behind it that puts an extra brake on it. In this way, now it is time to seek funding, wait for the experimental drugs to reach their own regulations and design a clinical trial to demonstrate whether this miracle in animals is also developed in humans and without intolerable side effects.
In short, it is a big step, yes. But the goal is still far away.
Images | Louis Reed RTVE
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