Apoptosis-Inducing TNF Superfamily Ligands for Cancer Therapy

SIMPLE SUMMARY: Cancer is a complicated disease that has a significant characteristic of evading cell death (apoptosis). The induction of apoptosis in cancerous cells seems a promising procedure to use as a cancer treatment. In the family of the tumor necrosis factor (TNF) proteins, there are some ligands with the capability to induce apoptosis. Several recombinant TNF apoptosis-inducing ligands have been designed over the years, and their characteristics have been improved. This review provides an overview of the studies done in different stages of the TNF apoptosis-inducing ligands as cancer treatments and the strategies to surpass their natural limitations to improve their effectiveness. ABSTRACT: Cancer is a complex disease with apoptosis evasion as one of its hallmarks; therefore, apoptosis induction in transformed cells seems a promising approach as a cancer treatment. TNF apoptosis-inducing ligands, which are naturally present in the body and possess tumoricidal activity, are attractive candidates. The most studied proteins are TNF-α, FasL, and TNF-related apoptosis-inducing ligand (TRAIL). Over the years, different recombinant TNF family-derived apoptosis-inducing ligands and agonists have been designed. Their stability, specificity, and half-life have been improved because most of the TNF ligands have the disadvantages of having a short half-life and affinity to more than one receptor. Here, we review the outlook on apoptosis-inducing ligands as cancer treatments in diverse preclinical and clinical stages and summarize strategies of overcoming their natural limitations to improve their effectiveness.