TNFSF10 and cancer: However, clinical testing of these first generation TRAIL-R agonists did not reveal meaningful anticancer activity in patients, likely owed to the combination of their limited agonistic activity [22, 29] and the fact that most cancers indeed exhibit primary resistance to apoptosis induction by TRAIL or other TRAIL-R agonists when used as single agents [16, 17, 29, 30].