For one of the most lethal tumors of all, a signal arrives that the scientific community has not seen for some time. In animal models, a new combination of three drugs managed to completely and lastingly regress pancreatic ductal adenocarcinoma, the most widespread and aggressive form of pancreatic cancer, maintaining the effect for over six months and with surprisingly low toxicity.
A sign of hope
The result comes from a work published in the scientific journal Proceedings of the National Academy of Sciences (Pnas) and conducted by the Experimental Oncology group of the Spanish National Center for Cancer Research (Cnio), led by Mariano Barbacid. This is not yet a cure, nor a result that can be immediately transferred to patients, but a proof of principle that could change the way in which one of the most difficult tumors to treat is addressed.
Pancreatic cancer has one of the worst prognoses in oncology: in most cases it is diagnosed at an advanced stage and responds poorly to available therapies. In recent decades, improvements have been limited, and only recently have the first drugs targeted against specific molecular targets arrived. However, the main problem remains resistance: even when therapies work initially, the tumor tends to find a way around them, growing again within a few months.
How the therapy works in mice
The strategy developed by the Spanish team aims to simultaneously target several fundamental mechanisms that allow tumor cells to survive and proliferate. The triple combination acts on the Kras gene, considered the main biological driver of pancreatic cancer and mutated in the vast majority of patients, and on two proteins, Egfr and Stat3, involved in the signals that favor tumor growth and the development of resistance to therapies.
According to the researchers, it is precisely this coordinated action on multiple fronts that has allowed them to obtain an unprecedented result in animal models. In treated mice, tumor regression was complete and maintained for approximately 200 days, a very long period in terms of preclinical testing, and without the severe side effects that often accompany aggressive cancer therapies.
Because (a lot of) caution is still necessary
However, Barbacid himself urges caution. At the moment, they explain from Cnio, there are not yet the conditions to start clinical trials on humans with this triple therapy. First, further steps will be needed to evaluate safety, dosages and possible side effects in depth, because what works in animal models does not always automatically translate into a benefit for patients.
The strongest value of the study, however, goes beyond the single finding. For a disease that has seen little significant progress for decades, this work demonstrates that overcoming drug resistance may require combined approaches, capable of anticipating the tumor’s biological “escape routes”. In recent years, the first drugs directed against Kras represented a historic turning point, but with benefits often limited in time. The idea of blocking multiple key nodes of the disease at the same time could now open a new phase of research.
It is not yet a cure and it is not yet a therapy for patients. But for one of the most aggressive tumors of all, this is some of the most promising preclinical evidence in recent years.