Researchers have examined pancreatic cancer cells and discovered an inverse correlation between the signatures of miR-34a, a tumour 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 aggressive cancer. The research team now needed to see if the same was true in humans.
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 tumour and prevents side effects in surrounding healthy tissues.
“We designed a nano-carrier 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,” said Professor Satchi-Fainaro, Chair of the Department of Physiology and Pharmacology at Tel Aviv University‘s Sackler Faculty of Medicine. “These were delivered directly to the tumour site to change the molecular signature of the cancer cells, rendering the tumour dormant or eradicating it altogether.
“The nanoparticle is like a taxi carrying two important passengers,” Prof. Satchi-Fainaro continues. “Many oncology protocols are cocktails, but the drugs usually do not reach a tumour at the same time. But our ‘taxi’ kept the ‘passengers’ — and the rest of the body — safe the whole way, targeting only the tumour 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 tumour cells.”