The promise of TRAIL--potential and risks of a novel anticancer therapy

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a biotherapeutic agent that induces apoptosis in cancer cells.
• TRAIL exhibits selectivity, primarily affecting tumor cells while sparing normal cells.
• TRAIL resistance is prevalent in primary human tumors, necessitating strategies for sensitization.

Purpose of the Study:

• To review the efficacy of TRAIL, alone or combined with chemotherapy, in inducing apoptosis in cancer cells.
• To compare the therapeutic effects of TRAIL on tumor cells versus its potential toxicity in normal tissues.
• To discuss various TRAIL formulations and their application in preclinical and clinical settings.

Main Methods:

• Review of preclinical studies on TRAIL's apoptosis-inducing pathways and efficacy.
• Analysis of in vitro tumor cell models and in vivo animal models.
• Evaluation of TRAIL in combination with chemotherapeutic drugs and irradiation.
• Discussion of recombinant TRAIL forms and agonistic antibodies targeting TRAIL death receptors.

Main Results:

• TRAIL effectively induces apoptosis in many tumor cell lines but shows resistance in primary tumors.
• Chemotherapy and irradiation can sensitize TRAIL-resistant cancer cells.
• Combinatorial TRAIL therapy demonstrates high efficacy in preclinical models with low toxicity to normal cells.
• Some studies report TRAIL-induced toxicity in normal cells, necessitating cautious clinical application.

Conclusions:

• TRAIL-based combination therapies show significant potential for cancer treatment.
• Further clinical studies are warranted to optimize TRAIL therapy and manage potential toxicities.
• TRAIL represents a promising therapeutic strategy, particularly when combined with other agents to overcome resistance and enhance safety.