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New Nanomedicine Could Prevent Progression of Pancreatic Cancer

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Israeli researchers discover survival rates in pancreatic cancer linked to inverse correlation between specific oncogene and tumor suppressant

A new study published in scientific journal Nature Communications distinguishes the reason for extended pancreatic cancer survival: an inverse correlation between a known oncogene, a gene that promotes the development of cancer, and the expression of an oncosuppressor microRNA.

The study may serve as a basis for the development of a medicine that can treat pancreatic and other cancers.

Though 75 percent of pancreatic cancer patients die within 12 months of diagnosis, about 7% survive more than five years. “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,” said lead researcher Prof. Ronit Satchi-Fainaro, chair of physiology and pharmacology at Tel Aviv University’s Sackler Faculty of Medicine.

She worked with Hadas Gibori and Shay Eliyahu, both members of her laboratory, 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 Chaim Sheba Medical Center at Tel Hashomer, Ramat Gan. Other authors of the paper include two researchers from The Institute for Drug Research in the Hebrew University of Jerusalem’s School of Pharmacy.

The research team examined pancreatic cancer cells in mouse models 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 made sense for such an aggressive cancer.

RNA profiling and analysis of samples taken by the researchers from pancreatic cancer patients revealed the same genomic pattern in humans as was seen in the mouse models.

Calling a nano-taxi

The scientists then devised a novel nanoparticle that selectively delivers genetic material to a tumor and prevents side effects in surrounding healthy tissues.

“The nanoparticle is like a taxi carrying two important passengers,” Satchi-Fainaro explained. “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.”

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. Theoretically, the same effect could be achieved in humans.

“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,” said Satchi-Fainaro.

The study was supported by the European Research Council, Tel Aviv University’s Cancer Biology Research Center and the Israel Science Foundation.

By: Rebecca Stadlen Amir
(Israel 21c)

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