Affiliations 

  • 1 School of Biosciences, Faculty of Science and Engineering, University of Nottingham Malaysia, 43500, Semenyih, Selangor, Malaysia
  • 2 Division of Biomedical Sciences, School of Pharmacy, University of Nottingham Malaysia, 43500, Semenyih, Selangor, Malaysia
  • 3 School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia; Advanced Engineering Platform, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia
  • 4 Medical Genetics Laboratory, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, 43400 UPM, Malaysia; UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Selangor, 43400 UPM, Malaysia
  • 5 School of Biosciences, Faculty of Science and Engineering, University of Nottingham Malaysia, 43500, Semenyih, Selangor, Malaysia. Electronic address: Eunice.Ngai@nottingham.edu.my
Crit Rev Oncol Hematol, 2019 Nov;143:81-94.
PMID: 31561055 DOI: 10.1016/j.critrevonc.2019.08.008

Abstract

Apoptosis is an ordered and orchestrated cellular process that occurs in physiological and pathological conditions. Resistance to apoptosis is a hallmark of virtually all malignancies. Despite being a cause of pathological conditions, apoptosis could be a promising target in cancer treatment. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), also known as Apo-2 ligand (Apo2L), is a member of TNF cytokine superfamily. It is a potent anti-cancer agent owing to its specific targeting towards cancerous cells, while sparing normal cells, to induce apoptosis. However, resistance occurs either intrinsically or after multiple treatments which may explain why cancer therapy fails. This review summarizes the apoptotic mechanisms via extrinsic and intrinsic apoptotic pathways, as well as the apoptotic resistance mechanisms. It also reviews the current clinically tested recombinant human TRAIL (rhTRAIL) and TRAIL receptor agonists (TRAs) against TRAIL-Receptors, TRAIL-R1 and TRAIL-R2, in which the outcomes of the clinical trials have not been satisfactory. Finally, this review discusses the current strategies in overcoming resistance to TRAIL-induced apoptosis in pre-clinical and clinical settings.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.