TRAIL-based therapeutic approaches for the treatment of pediatric malignancies

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells, offering a potential therapeutic advantage over conventional treatments.
• The tumor microenvironment significantly influences cancer development and elimination, impacting therapeutic efficacy.
• TRAIL-based therapies, including soluble TRAIL and antibodies targeting TRAIL receptors, aim to harness TRAIL's pro-apoptotic capabilities.

Purpose of the Study:

• To review the mechanisms of TRAIL-induced apoptosis, including extrinsic and intrinsic pathways, and its pro-survival signaling.
• To highlight resistance mechanisms to TRAIL-induced apoptosis and the rationale for combination therapies.
• To assess the potential of TRAIL-based therapies in pediatric malignancies and emerging cellular therapies.

Main Methods:

• Review of existing literature on TRAIL biology, cancer therapeutics, and clinical trial data.
• Analysis of preclinical data for TRAIL efficacy in various pediatric cancers.
• Exploration of emerging TRAIL-based cellular therapies.

Main Results:

• TRAIL effectively triggers apoptosis in diverse cancer cells with minimal toxicity to normal cells.
• Mechanisms of resistance, such as c-FLIP, Bcl-2, IAPs, p53, and NF-κB, can be targeted for combination therapies.
• Preclinical data suggest TRAIL's potential in pediatric malignancies like leukemia, lymphomas, and neuroblastoma.

Conclusions:

• TRAIL-based therapies represent a promising strategy for cancer treatment, particularly in pediatric malignancies.
• Combination approaches targeting resistance mechanisms are crucial for enhancing TRAIL efficacy.
• Emerging cellular therapies hold further potential for TRAIL-based cancer treatment.