Autophagy is an important survival mechanism of tumors. The Vps34 project is aimed at eliminating this mechanism in order that difficult to treat, resistant forms of cancer can be rendered treatable.

Biological Background

A cancer cell lives in a far tougher environment than a healthy cell and therefore must have effective systems for survival. Its rapid growth causes a shortage of both oxygen and nutrients. Treatment, both in the form of drugs and radiotherapy, causes damage to the cell. One of the survival systems is autophagy, and this helps keep the cells alive. By blocking a protein, Vps34, that is key to initiating autophagy, the tumor can be both weakened and made more sensitive to treatment.

Project Status

Sprint Bioscience have developed potent and selective inhibitors of Vps34 with good pharmaceutical properties. These compounds have been evaluated in cell-based systems where they block autophagy and kill cancer cells under stress. With a number of substances, we have shown that we can reduce tumor growth in an animal model of triple negative breast cancer. One of these, SB02024 has been selected for further profiling in pre-GLP toxicology studies prior to the selection of a clinical candidate.