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Among the leading causes of cancer deaths in the United States, pancreatic cancer represents a major threat to public health. This year, approximately 55,000 people in the United States will be diagnosed and more than 44,000 will die, making it one of the most deadly cancers. Currently, the five-year survival rate of pancreatic cancer is only 7% and the drugs to treat this aggressive disease are limited and numerous and ineffective.
However, researchers at Samuel Oschin's Comprehensive Cancer Institute at Cedars-Sinai may have found a reason to hope because the results of their new study show that a new drug, called Meavert, can prevent the type most common pancreatic cancer to develop. spread in laboratory mice. The results of this new study – recently published in Gastroenterology An article titled "An Inhibitor of GSK3B and HDAC Kills Pancreatic Cancer Cells and Slows Pancreatic Tumor Growth and Metastasis in Mice" – also demonstrated that Metavert could prevent patients from developing resistance to cancer chemotherapy. pancreas.
"It's an exciting step toward improving survival rates for patients with pancreatic cancer," says Mouad Edderkaoui, Ph.D., senior research scientist, assistant professor of medicine. and biomedical sciences at Cedars-Sinai. "If the results are confirmed in humans, we could have a drug with the potential to significantly prolong the lives of patients with pancreatic ductal adenocarcinoma (PDAC), which is very difficult to treat. "
Ninety-five percent of patients with pancreatic cancer are diagnosed with PDAC, which develops from cells lining small tubes in the pancreas. PDAC can be difficult to treat because cancer cells cause normal cells that reside in the pancreas, called stellate cells, to produce pancreatic scar tissue. Scar tissue makes it difficult for chemotherapy agents and blood to enter the pancreas.
The interaction between cancer and stellate cells also creates an environment that stimulates local tumor growth and spreads cancer to distant sites of the body. In addition, the activity levels of certain enzymes increase, promoting resistance to cancer treatments.
"Metavert significantly reduced PDAC cell survival but not untransformed cells; the agent reduced the markers of the epithelial transition to mesenchymal and stem cells in PDAC cell lines, "wrote the authors. "Cells incubated with metavert in combination with irradiation and paclitaxel or gemcitabine exhibited reduced survival compared to cells incubated with either or both agent alone; metavert increased the destruction of drug-resistant PDAC cells with paclitaxel and gemcitabine. PDAC cells incubated with metavert acquired a standardized glucose metabolism. The administration of metavert (alone or in combination with gemcitabine) to KPC mice or to mice with syngeneic tumors significantly increased their survival time, slowed tumor growth, prevented tumor metastasis, decreased tumor infiltration associated with
Over a four-year period, researchers have designed and synthesized new chemicals that inhibit the activity of cancer cells. They discovered that Metavert was blocking drug resistance and significantly increasing the positive effects of radiation and two commonly used chemotherapeutic agents in humans. In one of the mouse studies, Metavert increased the survival rate by about 50%.
"I saw patients who reacted to treatment for a while, then the disease took off because the cancer became smart – it blocks the way chemotherapy works," says Stephen Pandol, director of basic and translational pancreatic research at Cedars-Sinai. "Metavert targets this action."
The authors concluded that "in studies on PDAC cells and two mouse models of PDACs, we found a dual inhibitor of GSK3B and HDACS (metavert) to induce apoptosis of cancer cells, reduce migration, and reduce the risk of cancer." Expression of cell markers and slow tumor growth. metastases. Metavert has had synergistic effects with gemcitabine.
Currently, the Cedars-Sinai group is working to develop a version of the drug to be tested in humans.
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