Every single day, more than 1200 people around the world will hear these words: “You have been diagnosed with pancreatic cancer”. The prognosis is generally not good, with five-year survival rates being about 8%, but scientists from Cedars-Sinai are working on a groundbreaking drug that could change that.
In more than 90% of cases, patients develop pancreatic ductal adenocarcinoma (PDAC), an aggressive and fast-growing form of malignancy that is particularly resistant to chemotherapy. It starts off in the lining of the organ and it prompts normal cells (or stellate cells) to produce pancreatic scar tissue making treatment considerably difficult.
The study details how the team managed to design and synthesize a compound that inhibits glycogen synthase kinase 3 beta (GSK3B) and histone deacetylases (HCACs), two markers closely associated with PDAC.
Named Metavert, the drug showed remarkable effectiveness when tested on pancreatic cancer cells and mice with pancreatic tumors. During the last four years since the project was started, investigators found that the compound “blocked drug resistance and also significantly boosted the positive effects of radiation and two chemotherapy agents commonly used in humans”, paclitaxel and gemcitabine.
“This is an exciting step toward improving survival rates in pancreatic cancer patients”, said Mouad Edderkaoui, Ph.D., assistant professor of Medicine and Biomedical Sciences at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai and study leader.
In one of the mouse trials, Metavert produced survival rates of about 50 percent. Overall, it “significantly increased their survival times, slowed tumor growth, prevented tumor metastasis, decreased tumor infiltration by tumor-associated macrophages, and decreased blood levels of cytokines”.
These findings generated a lot of excitement and optimism for future treatments, and Dr. Edderkaoui added: “If the results are confirmed in humans, we could have a drug with the potential to significantly extend the lives of patients with pancreatic ductal adenocarcinoma (PDAC), which is very difficult to treat”.