Death Receptor–Ligand Systems in Cancer, Cell Death, and Inflammation

Abstract

The discovery of tumor necrosis factor (TNF) marked the beginning of one of the most fascinating journeys in modern biomedical research. For the moment, this journey has culminated in the development of drugs that inhibit TNF. TNF blockers have revolutionized the treatment of many chronic inflammatory diseases. Yet, the journey seems far from over. TNF is the founding member of a family of cytokines with crucial functions in cell death, inflammation, and cancer. Some of these factors, most prominently TNF, CD95L, and TRAIL, can induce cell death. The receptors that mediate this signal are therefore referred to as death receptors, even though they also activate other signals. Here I will take you on a journey into the discovery and study of death receptor-ligand systems and how this inspired new concepts in cancer therapy and our current understanding of the interplay between cell death and inflammation.