Survival rates in pancreatic cancer linked to inverse correlation between specific oncogene and tumor suppressant
A new Tel Aviv University study pinpoints the inverse correlation between a known oncogene — a gene that promotes the development of cancer — and the expression of an oncosuppressor microRNA as the reason for extended pancreatic cancer survival. The study may serve as a basis for the development of an effective cocktail of drugs for this deadly disease and other cancers.
The study, which was published in Nature Communications, was led by Prof. Ronit Satchi-Fainaro, Chair of the Department of Physiology and Pharmacology at TAU’s Sackler Faculty of Medicine, and conducted by Hadas Gibori and Dr. Shay Eliyahu, both of Prof. Satchi-Fainaro’s multidisciplinary 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 Golanof Chaim Sheba Medical Center, Tel Hashomer.
Pancreatic cancer is among the most aggressive cancers known today. The overwhelming majority of pancreatic cancer patients die within just 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,” Prof. Satchi-Fainaro says.
“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,” Prof. Satchi-Fainaro continues. “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.”
Calling a nano-taxi
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 made sense for such an aggressive cancer. But the team 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 tumor and prevents side effects in surrounding healthy tissues.
“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,” Prof. Satchi-Fainaro says. “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,” Prof. Satchi-Fainaro continues. “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
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.
“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,” according to Prof. Satchi-Fainaro.
The Latest on: Pancreatic cancer
- How to Treat Pancreatic Cancer on February 15, 2019 at 10:15 am
There is no way to sugarcoat the fact that pancreatic cancer is very difficult to treat. Only about 20 to 30 percent of cases are found early enough to treat surgically, before the cancer has ... […]
- Following lung cancer surgery, Supreme Court Justice Ruth Bader Ginsburg back at work on February 15, 2019 at 8:43 am
She underwent surgery for colorectal cancer in 1999 and early-stage pancreatic cancer in 2009. The Supreme Court said Justice Ruth Bader Ginsburg has returned to work at the building for the first tim... […]
- Supreme Court Justice Ginsburg back at court after cancer bout on February 15, 2019 at 7:50 am
Ginsburg was treated in 1999 for colon cancer and again in 2009 for pancreatic cancer but did not miss any argument sessions either time. In 2014, doctors placed a stent in her right coronary artery t... […]
- Judge elected in historic group of 17 black female judges dies one week after pancreatic cancer diagnosis on February 14, 2019 at 11:59 am
Hollemon's daughter, Brandy Hollemon, confirmed to the Associated Press that her mother died Monday at age 57. "She was an awesome, very strong woman," Brandy Hollemon said. Cassandra Hollemon was par... […]
- Judge dies week after pancreatic cancer diagnosis, still came to work on February 14, 2019 at 8:04 am
Harris County Judge Cassandra Holleman only got to serve one full month on the bench before pancreatic cancer claimed her life. RELATED: Newly elected Harris County misdemeanor judge has died "I ... […]
- Pancreatic Cancer Pipeline Review H1 2019 on February 14, 2019 at 3:09 am
Publisher's latest Pharmaceutical and Healthcare disease pipeline guide Pancreatic Cancer - Pipeline Review, H1 2017, provides an overview of the Pancreatic Cancer (Oncology) pipeline landscape. Pancr... […]
- Health Beat: Chinese tree bark treats pancreatic cancer on February 13, 2019 at 1:47 pm
BUFFALO - Michael Gilkerson doesn't miss a day on his treadmill. He said it gives him strength and motivation after being diagnosed with pancreatic cancer more than two years ago. "I've never told my ... […]
- USPSTF Still Recommends Against Pancreatic Cancer Screening on February 13, 2019 at 11:18 am
(HealthDay News) -- The U.S. Preventive Services Task Force (USPSTF) recommends against screening for pancreatic cancer in asymptomatic adults. These findings form the basis of a draft recommendation ... […]
- Fisetin induces autophagy in pancreatic cancer cells via endoplasmic reticulum stress- and mitochondrial stress-dependent pathways on February 13, 2019 at 2:52 am
Pancreatic cancer is one of the most aggressive tumors and patients have poor survival rates. Fisetin, a natural flavonoid, was recently reported to have antitumor effects in various cancer models. Au... […]
- Drug made from Chinese tree bark offers hope for pancreatic cancer patients on February 11, 2019 at 3:32 pm
BUFFALO, N.Y. - Researchers are finding new hope in an ancient remedy to treat pancreatic cancer. Pancreatic cancer is one of the toughest cancers to treat. Only 6 to 8 percent of patients survive fiv... […]
via Google News and Bing News