According to the Cancer Observatory of the Spanish Association against Cancer (AECC), pancreatic cancer is somewhat more common among men than among women and about 8,000 new cases are registered each year in Spain. Unfortunately, despite significant progress in this field, it continues to have a poor prognosis.
Now, a team of Spanish researchers led by biochemist Mariano Barbacid from the National Center for Oncological Research (CNIO) has achieved for the first time the complete disappearance of advanced pancreatic cancer in mice.
The study, published in the journal Cancer Cell , has focused on ductal adenocarcinoma of the pancreas (ADP), one of the most aggressive forms of cancer and the most resistant to current treatments (practically its cure is limited to those cases in those in which the tumor is localized and can be surgically removed, something that occurs in only 10% of patients).
“We have developed a new generation of genetically modified mouse models that have made it possible to evaluate the therapeutic effect of molecular targets in carriers of advanced tumors and to identify possible toxic effects by eliminating or inhibiting these targets systemically throughout the body”, clarifies Barbacid .
The researchers evaluated the therapeutic potential of two targets involved in KRAS oncoprotein signaling: epidermal growth factor receptor, EGFR, and c-RAF kinase. For the experiment, they used a group of genetically modified mice, induced by the same mutations responsible for most human tumors (KRAS and TP53), and which reproduce the usual path of these tumors quite well.
The experiment resulted in the complete disappearance in mice of advanced pancreatic cancer, that is, throughout the body and after a few weeks, the tumor cells completely disappeared. Until now, the disappearance (complete regression) of advanced pancreatic cancer has never been observed in any experimental model, which is a great medical milestone.
There will be a clinical delay
The result, despite being tremendously hopeful, will take some time to reach clinical trials, since currently there are no inhibitors capable of blocking the activity of c-RAF in this type of tumor. And if there were, they would be highly toxic, so it is not possible to reproduce them pharmacologically.
It is important to note that not all tumors, both murine – special strains of mice to analyze a human disease or condition – and humans, responded to this therapy, an extreme that highlights the great variety that pancreatic ductal adenocarcinoma presents.
The transcriptional profiling studies reported in the Barbacid team’s study showed differences in the expression of more than 2,000 genes between the responding and non-responding tumors.
Reference: Blasco et al .: Complete Regression of Advanced Pancreatic Ductal Adenocarcinomas upon Combined Inhibition of EGFR and C-RAF. Cancer Cell DOI: 10.1016 / j.ccell.2019.03.002
