Perspektywy rozwoju strategii terapeutycznych opartych na TRAIL i jego analogach w hematoonkologii

TRAIL (TNF-related apoptosis inducing ligand), member of the tumor necrosis factor superfamily, is known for its strong antitumor activity in many types of cancer cells, while exhibiting relatively low cytotoxicity to most normal cells. Therapeutic strategies utilizing TRAIL or its analogs usually exhibit high activity in preclinical in vitro and in vivo models. In clinical trials, TRAIL and its analogs were generally well tolerated, but, surprisingly, exhibited low activity. Major limitation of TRAIL-based therapies is intrinsic or secondary resistance to apoptosis induction, mediated by a plethora of diverse mechanisms. However, as at least a fraction of these resistance mechanisms are amenable for pharmacological modulation, they represent rational targets for combination therapies synergizing with TRAIL. Herein, we review the preclinical and clinical trials based on combination of pharmaceutics synergizing with TRAIL or TRAIL analogs and discuss the prospects of development of such strategies.