New hopes for a cure for pancreatic cancer from Italian research. A study by the European Institute of Oncology (IEO) in Milan, supported by the Airc Foundation and published in 'Sciences Advances', places “the molecular basis for effective combined therapy“, announces the Irccs founded by Umberto Veronesi. The mix combines a target therapy with immunotherapy: “Individually not very effective, if combined they obtain a good therapeutic result”, explain the authors coordinated by Gioacchino Natoli of the Ieo Department of Molecular Oncology “Together, in preclinical models they have demonstrated that they can acquire very significant control of the disease”, point out the scientists who, thanks to this work, also see the possibility of therapeutic vaccines on the horizon.
The Pancreatic cancer is characterized by a set of very well-defined DNA mutations, recalls an IEO note. Among the best known are the mutations of the Kras gene, whose protein products mimic constant and abnormal stimulation by growth factors, thus inducing uncontrolled proliferation of cells. Some molecularly targeted drugs have been tested against these mutations, designed precisely to counteract these effects. However, attempts to specifically block the transmission of proliferative stimuli induced by the Kras mutation, in particular with the inhibitor trametinib, have so far not produced the expected therapeutic results.
“We used advanced genomic and computational analysis procedures – explains Natoli – to determine the reasons for the surprising resistance of pancreatic cancer cells to trametinib. This analysis showed a surprising effect: even if trametinib does not significantly slow down the growth of tumor cells , however, activates mechanisms that can make them targets of an immune response. On the basis of these data, in collaboration with Andrea Viale's group at the MD Anderson Cancer Center in Houston, we evaluated the therapeutic effect of the combination of trametinib with drugs that increase the immune response against tumors, the so-called immune checkpoint inhibitors, achieving significant therapeutic effects”.
The researchers, the note explains, have discovered that trametinib induces the expression of endogenous retroviruses in pancreatic cancer cells. These retroviruses are pieces of viral genetic material that inserted themselves into the mammalian genome during infections possibly dating back hundreds of thousands or even millions of years. They belong to that very large part of the human genome which is considered devoid of function and which for this reason has also been called junk DNA. Normally these portions of ancient viral DNA are 'silenced' in the human body and are therefore effectively inert and without a role. If activated, however, endogenous retroviruses simulate a viral infection and cells expressing them are detected by the immune system in the same way as cells infected by viruses today. As a result, the immune system reacts by attacking tumor cells that express endogenous retroviruses, thus destroying the tumor.
“This new approach – comments Alice Cortesi, first author of the article – opens the way to a rational combination of treatments that could prove very effective in fighting pancreatic cancer. Furthermore, the activation of endogenous retroviruses induced by trametinib could provide new targets for the development of therapeutic vaccines also against pancreatic cancer. Now we need to have confirmation of the data obtained in the laboratory in the context of upcoming clinical studies, which we hope to be able to activate as quickly as possible”.
#Pancreatic #cancer #hopes #cure #synergy #immunotherapy #targeted #drugs
