TRAIL pathway targeting therapeutics

ABSTRACT

Introduction: Despite decades of focused research efforts, cancer remains a significant cause of morbidity and mortality. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is capable of inducing cell death selectively in cancer cells while sparing normal cells.

Areas covered: In this review, the authors cover TRA therapy and strategies that have been undertaken to improve their efficacy, as well as unconventional approaches to TRAIL pathway activation including TRAIL-inducing small molecules. They also discuss mechanisms of resistance to TRAIL and the use of combination strategies to overcome it.

Expert commentary: Targeting the TRAIL pathway has been of interest in oncology, and although initial clinical trials of TRAIL receptor agonists showed limitations, novel approaches represent the future of TRAIL-based therapy.

KEYWORDS:

• Apoptosis
• cancer
• TRAIL

Declaration of interest

WS El-Deiry is a co-Founder and shareholder in Oncoceutics, a company that is developing ONC201 in the clinic. WS El-Deiry is compliant with institutional and NIH disclosure guidelines. Oncoceutics provided no financial support for the review and has not been involved in any way in its writing. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This article was funded by NIH grant [R01 CA173453].