TAU researchers find way to inhibit progression of pancreatic cancer in mice

A novel technique using nanomedicine inhibits the progression of pancreatic cancer in mice, according to research at Tel Aviv University.Prof. Ronit Satchi-Fainaro, chairman of the physiology and pharmacology department at TAU’s Sackler Faculty of Medicine who led the team, has just published their findings in the prestigious journal Nature Communications. Her team included Hadas Gibori and Dr. Shay Eliyahu, working in collaboration with Prof.Eytan Ruppin of TAU’s computer science department and the University of Maryland, and Prof. Iris Barshack and Dr.Talia Golan of Sheba Medical Center at Tel Hashomer.They identified the reason for certain patients’ extended survival from the pernicious malignancy as being related to the inverse correlation between a known oncogene – a gene that promotes the development of cancer – and the expression of an oncosuppressor microRNA.The study, said Satchi-Fainaro, could serve as a basis for the development of an effective cocktail of drugs for this deadly disease and other cancers.Pancreatic cancer is among the most aggressive cancers known today. The overwhelming majority of pancreatic cancer patients die within a year of diagnosis. “Despite all the treatments afforded by modern medicine, some 57% of all pancreatic cancer patients die within 21 months of diagnosis, including many who die within just a few months,” she said.But around 7% of those diagnosed will survive more than five years. “We sought to examine what distinguishes the survivors from the rest of the patients,” Satchi-Fainaro continued.“We thought that if we could understand how some people live several years with this most aggressive disease, we might be able to develop a new therapeutic strategy.”The research team examined pancreatic cancer cells and discovered an inverse correlation between the signatures of miR-34a, a tumor suppressant, and PLK1, a known oncogene.The levels of miR-34a were low in pancreatic cancer mouse models, while the levels of the oncogene were high. This correlation seemed logical for such an aggressive cancer, but the researchers needed to see if it was relevant in humans as well as mice.The scientists performed RNA profiling and analysis of samples taken from pancreatic cancer patients; the molecular profiling revealed the same genomic pattern found earlier in mouse models of pancreatic cancer. The scientists then devised a novel nanoparticle that selectively delivers genetic material to a tumor and prevents side effects in surrounding healthy tissues.“We designed a nanocarrier to deliver two passengers: miR- 34a, which degrades hundreds of oncogenes; and a PLK1 small interfering RNA (siRNA), that silences a single gene,” Satchi- Fainaro noted. “These were delivered directly to the tumor site to change the molecular signature of the cancer cells, rendering the tumor dormant or eradicating it altogether,” she said.“The nanoparticle is like a taxi carrying two important passengers,” Satchi-Fainaro continued. “Many oncology protocols are cocktails, but the drugs usually do not reach the tumor at the same time. But our ‘taxi’ kept the ‘passengers’ – and the rest of the body – safe the whole way, targeting only the tumor tissue. Once it ‘parked,’ an enzyme present in the tumor caused the carrier to biodegrade, allowing the therapeutic cargo to be released at the correct address – the tumor cells.”To validate their findings, the scientists injected the novel nanoparticles into pancreatic tumor-bearing mice and observed that by balancing these two targets – bringing them to a normal level by increasing their expression or blocking the gene responsible for their expression – they significantly prolonged the survival of the mice.