TY - JOUR
T1 - The TRAIL to cancer therapy
T2 - Hindrances and potential solutions
AU - Wong, Sonia How Ming
AU - Kong, Wei Yang
AU - Fang, Chee Mun
AU - Loh, Hwei San
AU - Chuah, Lay Hong
AU - Abdullah, Syahril
AU - Ngai, Siew Ching
N1 - Funding Information:
This work was supported by Fundamental Research Grant Scheme (FRGS/1/2016/STG05/UNIM/03/1), funded by the Ministry of Education Malaysia .
Publisher Copyright:
© 2019 Elsevier B.V.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/11
Y1 - 2019/11
N2 - 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.
AB - 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.
KW - Cancer therapy
KW - Resistance
KW - TRAIL
UR - http://www.scopus.com/inward/record.url?scp=85072523027&partnerID=8YFLogxK
U2 - 10.1016/j.critrevonc.2019.08.008
DO - 10.1016/j.critrevonc.2019.08.008
M3 - Review Article
C2 - 31561055
AN - SCOPUS:85072523027
SN - 1040-8428
VL - 143
SP - 81
EP - 94
JO - Critical Reviews in Oncology/Hematology
JF - Critical Reviews in Oncology/Hematology
ER -
