A compact synthetic pathway rewires cancer signaling to therapeutic effector release

Abstract

Seeking and destroying cancer cells Rather than inhibiting aberrant signaling in cancer cells, what if that signal was put to work in detecting and destroying the cancer cells? Such an anticancer strategy could be based on the ErbB family of receptors that is activated in many cancers. Chung et al. developed a cell-killing circuit that is activated by excessive ErbB signaling and used a viral delivery system to add it to cells. The ErbB receptor proteins are tyrosine kinases that autophosphorylate. The authors designed a protease that would be recruited to such over-phosphorylated receptors. Once in place, the protease cleaves a protein anchored to the cell membrane, releasing it into the cytoplasm where it causes death of the transformed cells. Science , this issue p. eaat6982