Revisiting the role of TRAIL/TRAIL-R in cancer biology and therapy.
Deepika SinghMallika TewariSunita SinghGopeshwar NarayanPublished in: Future oncology (London, England) (2021)
TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, can induce apoptosis in cancer cells, sparing normal cells when bound to its associated death receptors (DR4/DR5). This unique mechanism makes TRAIL a potential anticancer therapeutic agent. However, clinical trials of recombinant TRAIL protein and TRAIL receptor agonist monoclonal antibodies have shown disappointing results due to its short half-life, poor pharmacokinetics and the resistance of the cancer cells. This review summarizes TRAIL-induced apoptotic and survival pathways as well as mechanisms leading to apoptotic resistance. Recent development of methods to overcome cancer cell resistance to TRAIL-induced apoptosis, such as protein modification, combination therapy and TRAIL-based gene therapy, appear promising. We also discuss the challenges and opportunities in the development of TRAIL-based therapies for the treatment of human cancers.
Keyphrases
- induced apoptosis
- endoplasmic reticulum stress
- cell death
- combination therapy
- oxidative stress
- cell cycle arrest
- clinical trial
- rheumatoid arthritis
- signaling pathway
- randomized controlled trial
- endothelial cells
- stem cells
- protein protein
- small molecule
- squamous cell carcinoma
- binding protein
- study protocol
- diabetic rats
- editorial comment
- cell therapy
- minimally invasive
- smoking cessation