Researchers from University of Colorado, lead by Antonio Jimeno, have found that, a new drug, Rigosertib, allows pancreatic cancer cells to rush through replication - and then stops them cold, killing them in in the middle of a step called M phase. Healthy cells that don't rush are unharmed.
Data from a phase I clinical trial of patients with advanced pancreatic cancer and additional solid tumors recently published in the journal Clinical Cancer Research shows the strategy has promise. While the goal of any phase I trial is to establish the dosage that best balances effectiveness against side effects, 11 of the 19 patients treated achieved stable disease, which lasted for a median of 113 days.
"Really, the drug takes one of cancer's greatest strengths and turns it into a weakness," says Wells Messersmith, MD, co-leader of the Developmental Therapeutics Program at the University of Colorado Cancer Center and the clinical trial's national principal investigator.
Instead of going with the flow of the natural cell cycle, cancer cells amplify two signals - PLK1 and PI3K - which allows them to blast through the cell cycle and divide much more quickly. In the process, they break this step of the natural cell cycle, known as the G1 regulatory mechanism, and thus depend on the kick of PLK1 and P13K to push at a frenzied pace through replication...