New Cancer Drug Developed to Starve Off Cancer Cells

Treatment could make existing cancer drugs more effective.

Scientists at Salk Institute and Sanford Burnham Prebys Medical Discovery Institute have developed a cancer drug that stops the process of autophagy in defective cells.

Autophagy is a cell process to recycle decaying organelles. Cancerous cells use these recycled nutrients to multiply quickly, making autophagy an important element in the spread of cancer. Cell misuse of autophagy is also connected to numerous infectious diseases, neurodenegeration, and heart problems.

At SBP, Reuben Shaw, PhD, and his team have isolated the enzyme that starts autophagy, ULK1, and have developed the drug SBI-0206965 to turn it off. By shutting off ULK1, autophagy cannot begin, and cancer cells eventually starve off and die.

Shaw's team and Nicholas Cosford, PhD, who studied the ULK1 enzyme, created the drug, which in clinical trials killed brain cancer cells in humans and lung cancer cells in mice to great success.

SBI-0206965 is not the first drug to target autophagy. One drug managed to inhibit lysosomes in cells, which is crucial in the final stage of autophagy. However, targeting organelles also inhibits them from carrying out important functions, thus creating adverse side effects. SBI-0206965 manages to shut off autophagy without harming other organelles.

"Inhibiting ULK1 would eliminate this last-ditch survival mechanism in the cancer cells and could make existing anti-cancer treatments much more effective," says Matthew Chun, one of the study's lead authors and a postdoctoral fellow in the Shaw lab at Salk.

When combined with other cancer drugs, like mTOR inhibitors, SBI-0206965 killed two to three times as many lung cancer cells in mice. Currently, the team is testing the drug's reaction with other types of mouse cancers, and testing it with other kinds of therapy.

This study was originally published in the June 2015 issue of Molecular Cell.