Innovative research conducted at Tel Aviv University indicates that extended pancreatic cancer survival is enabled by an inverse correlation between an oncogene (a gene promoting cancer development) and the signatures of an oncosuppressor microRNA.
This research might be used as the foundation for developing an effective mix of drugs not only for pancreatic cancer, but also for other types of cancers.
Professor Ronit Satchi-Fainaro, Chair of the Department of Physiology and Pharmacology at TAU’s Sackler Faculty of Medicine, headed the research, which was performed by Hadas Gibori and Dr. Shay Eliyahu, both from Professor Satchi-Fainaro’s multidisciplinary laboratory. It was carried out in cooperation with Professor Eytan Ruppin from TAU’s Computer Science Department and the University of Maryland, and Professor Iris Barshack and Dr. Talia Golan from Chaim Sheba Medical Center, Tel Hashomer. The study has been reported in the Nature Communications journal.
Pancreatic cancer is one of the deadliest cancers. Most of the patients suffering from pancreatic cancer die within a year of diagnosis.
Despite all the treatments afforded by modern medicine, some 75% of all pancreatic cancer patients die within 12 months of diagnosis, including many who die within just a few months. But around seven percent of those diagnosed will survive more than five years. We sought to examine what distinguishes the survivors from the rest of the patients. 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.
Professor Ronit Satchi-Fainaro, Chair of the Department of Physiology and Pharmacology at TAU’s Sackler Faculty of Medicine
Calling a nano-taxi
The researchers investigated pancreatic cancer cells and found out that an inverse correlation exists between PLK1, a known oncogene, and the expression of miR-34a, a tumor suppressant. The oncogene levels were high in pancreatic cancer mouse models, while the levels of miR-34a were low. Researchers wanted to explore whether it was also the same in humans.
The team carried out RNA profiling and investigated samples taken from patients suffering from pancreatic cancer. The molecular profiling exhibited the same genomic pattern already found in mouse models for pancreatic cancer.
The researchers then developed an innovative nanoparticle that selectively administers genetic material to a tumor and eliminates side effects to healthy tissues surrounding the tumor.
“We designed a nanocarrier to deliver two passengers: (1) miR-34a, which degrades hundreds of oncogenes; and (2) a PLK1 small interfering RNA (siRNA), that silences a single gene,” stated Professor Satchi-Fainaro. “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.”
“The nanoparticle is like a taxi carrying two important passengers,” continued Professor Satchi-Fainaro. “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 pancreatic cancer caused the carrier to biodegrade, allowing the therapeutic cargo to be released at the correct address—the tumor cells.”
Improving the odds
In order to prove the outcomes of the study, the researchers administered the innovative nanoparticles into mice bearing pancreatic tumor and found that when the two targets were balanced—getting them to a normal level by increasing their signatures or blocking the gene responsible for their signatures—they considerably lengthened the survival period of the mice.
“This treatment takes into account the entire genomic pattern, and shows that affecting a single gene is not enough for the treatment of pancreatic cancer or any cancer type in general,” stated Professor Satchi-Fainaro.
The European Research Council (ERC), Tel Aviv University’s Cancer Biology Research Center (CBRC), and the Israel Science Foundation (ISF) funded the study.