RETRACTED: Harnessing TRAIL-Induced Apoptosis Pathway for Cancer Immunotherapy and Associated Challenges

Abstract

The immune cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted rapidly evolving attention as a cancer treatment modality because of its competence to selectively eliminate tumor cells without instigating toxicity in vivo. TRAIL has revealed encouraging promise in preclinical reports in animal models as a cancer treatment option; however, the foremost constraint of the TRAIL therapy is the advancement of TRAIL resistance through a myriad of mechanisms in tumor cells. Investigations have documented that improvement of the expression of anti-apoptotic proteins and survival or proliferation involved signaling pathways concurrently suppressing the expression of pro-apoptotic proteins along with down-regulation of expression of TRAILR1 and TRAILR2, also known as death receptor 4 and 5 (DR4/5) are reliable for tumor cells resistance to TRAIL. Therefore, it seems that the development of a therapeutic approach for overcoming TRAIL resistance is of paramount importance. Studies currently have shown that combined treatment with anti-tumor agents, ranging from synthetic agents to natural products, and TRAIL could result in induction of apoptosis in TRAIL-resistant cells. Also, human mesenchymal stem/stromal cells (MSCs) engineered to generate and deliver TRAIL can provide both targeted and continued delivery of this apoptosis-inducing cytokine. Similarly, nanoparticle (NPs)-based TRAIL delivery offers novel platforms to defeat barricades to TRAIL therapeutic delivery. In the current review, we will focus on underlying mechanisms contributed to inducing resistance to TRAIL in tumor cells, and also discuss recent findings concerning the therapeutic efficacy of combined treatment of TRAIL with other antitumor compounds, and also TRAIL-delivery using human MSCs and NPs to overcome tumor cells resistance to TRAIL.

TRAIL-Based Therapies Efficacy in Pediatric Bone Tumors Models Is Modulated by TRAIL Non-Apoptotic Pathway Activation via RIPK1 Recruitment

“…We, here, provided important insights into: (1) the role played by the non-apoptotic pathways induced by TRAIL in the resistance of this model to the DR5-agonist AMG655; (2) the validation of TRAIL-based therapies in pediatric bone tumors; and (3) the proof of concept for new adjuvant targets that can synergize with TRAIL receptors agonists. Several synergies have already been described in the literature [ 40 ], here we can suggest, for example, Necrostatine-1 that inhibits RIPK1 kinase activity [ 41 , 42 ]. This compound has already demonstrated therapeutic interest thanks to its ability to inhibit TRAIL-induced necroptosis by acidic pH in liver and colon cancer cell lines [ 43 ].…”

Serum multi-cytokines screening identifies TRAIL and IL-10 as probable new biomarkers for prostate health index diagnostic utility adjustment in grey zone aggressive prostate cancer detection: A single-center data in China

“…Functioning as one of the tumor necrosis factor ligand family, TRAIL has been reported to induce apoptosis in tumor cells preferentially. Recent studies have reported that targeting TRAIL is a promising anticancer therapy for prostate cancer, and harnessing TRAIL-induced apoptosis pathway for immunotherapy has attracted attention rapidly as a cancer treatment target ( 27 , 28 ). However, the existing reports on TRAIL are focusing on the function of tumor cell apoptosis induction, and no study on diagnostic biomarker value for PCa has been proposed.…”

A novel tumor-homing TRAIL variant eradicates tumor xenografts of refractory colorectal cancer cells in combination with tumor cell-targeted photodynamic therapy

“…As TRAIL induces apoptosis of tumor cells by triggering DRs, the sensitivity of tumor cells to TRAIL is usually proportional to the level of DRs expressed on these cells (Wong, 2011 ; Di et al., 2013 ; Razeghian et al., 2021 ). In fact, COLO205 cells expressed more DR4 and DR5 than HT29 cells ( Figure 1(B) ).…”