Targeting TRAIL

Ion, George; Nițulescu, George Mihai; Popescu, Costin I.

doi:10.1016/j.bmcl.2019.07.053

Cited by 9 publications

(5 citation statements)

References 105 publications

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“…Current data underline a complex impact of these factors on tumorigenesis and cancer therapy [100][101][102]. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is able to selectively induce apoptosis in cancer cells [103]. Moreover, interferon-gamma (IFN-gamma) can protect against tumor development, affecting both innate and adaptive host immune responses [104].…”

Section: Signaling By Cytokines Chemokines and Growth Factorsmentioning

confidence: 99%

Communication in the Cancer Microenvironment as a Target for Therapeutic Interventions

Dominiak

Chełstowska

Olejarz

et al. 2020

Cancers

114

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The tumor microenvironment (TME) is a complex system composed of multiple cells, such as non-cancerous fibroblasts, adipocytes, immune and vascular cells, as well as signal molecules and mediators. Tumor cells recruit and reprogram other cells to produce factors that maintain tumor growth. Communication between cancerous and surrounding cells is a two-way process and engages a diverse range of mechanisms that, in consequence, can lead to rapid proliferation, metastasis, and drug resistance, or can serve as a tumors-suppressor, e.g., through tumor–immune cell interaction. Cross-talk within the cancer microenvironment can be direct by cell-to-cell contact via adhesion molecules, electrical coupling, and passage through gap junctions, or indirect through classical paracrine signaling by cytokines, growth factors, and extracellular vesicles. Therapeutic approaches for modulation of cell-cell communication may be a promising strategy to combat tumors. In particular, integrative approaches targeting tumor communication in combination with conventional chemotherapy seem reasonable. Currently, special attention is paid to suppressing the formation of open-ended channels as well as blocking exosome production or ablating their cargos. However, many aspects of cell-to-cell communication have yet to be clarified, and, in particular, more work is needed in regard to mechanisms of bidirectional signal transfer. Finally, it seems that some interactions in TEM can be not only cancer-specific, but also patient-specific, and their recognition would help to predict patient response to therapy.

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Section: Signaling By Cytokines Chemokines and Growth Factorsmentioning

confidence: 99%

Communication in the Cancer Microenvironment as a Target for Therapeutic Interventions

Dominiak

Chełstowska

Olejarz

et al. 2020

Cancers

114

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“…However, and more importantly, employing photothermal therapy (PTT) by photoabsorber Ph556 converting light to heat for tumor thermal ablation caused a synergistic effect between IPN nanoparticles and wrapped TRAIL protein by upregulating the expression of the TRAIL death receptors DR4 and DR5, resulting in the synergistic effects between PTT and TRAIL therapy. Usually, chemotherapeutic agents are used to upregulate the expression of death receptors DR4 and DR5 in cancer cells [ 96 ]. The remodeling of the death receptor expression by PTT is stated as safer and more controllable compared to chemotherapy [ 95 ].…”

Section: Polymer-based Systems For Nanodelivery Of Trail Pathway-targ...mentioning

confidence: 99%

Recent Advances in the Development of Nanodelivery Systems Targeting the TRAIL Death Receptor Pathway

2023

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The TRAIL (TNF-related apoptosis-inducing ligand) apoptotic pathway is extensively exploited in the development of targeted antitumor therapy due to TRAIL specificity towards its cognate receptors, namely death receptors DR4 and DR5. Although therapies targeting the TRAIL pathway have encountered many obstacles in attempts at clinical implementation for cancer treatment, the unique features of the TRAIL signaling pathway continue to attract the attention of researchers. Special attention is paid to the design of novel nanoscaled delivery systems, primarily aimed at increasing the valency of the ligand for improved death receptor clustering that enhances apoptotic signaling. Optionally, complex nanoformulations can allow the encapsulation of several therapeutic molecules for a combined synergistic effect, for example, chemotherapeutic agents or photosensitizers. Scaffolds for the developed nanodelivery systems are fabricated by a wide range of conventional clinically approved materials and innovative ones, including metals, carbon, lipids, polymers, nanogels, protein nanocages, virus-based nanoparticles, dendrimers, DNA origami nanostructures, and their complex combinations. Most nanotherapeutics targeting the TRAIL pathway are aimed at tumor therapy and theranostics. However, given the wide spectrum of action of TRAIL due to its natural role in immune system homeostasis, other therapeutic areas are also involved, such as liver fibrosis, rheumatoid arthritis, Alzheimer’s disease, and inflammatory diseases caused by bacterial infections. This review summarizes the recent innovative developments in the design of nanodelivery systems modified with TRAIL pathway-targeting ligands.

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“…TRAIL is an interesting therapeutic target, as it preferentially targets tumor cells and shows low levels of toxicity in animal models [ 84 ]. TRAIL agonists such as recombinant TRAIL, TRAIL-R antibodies, fusion proteins, and small molecules are being investigated preclinically in various malignancies, including DLBCL [ 97 , 98 ]. In addition, the TRAIL receptor agonist ABBV-621 is currently being investigated in a phase I clinical trial in solid tumors and hematological malignancies (NCT03082209; Supplementary Table S1 ).…”

Section: Extrinsic Apoptotic Pathwaymentioning

confidence: 99%

Genetic Events Inhibiting Apoptosis in Diffuse Large B Cell Lymphoma

Léveillé

Johnson

2021

Cancers

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Diffuse large B cell lymphoma (DLBCL) is curable with chemoimmunotherapy in ~65% of patients. One of the hallmarks of the pathogenesis and resistance to therapy in DLBCL is inhibition of apoptosis, which allows malignant cells to survive and acquire further alterations. Inhibition of apoptosis can be the result of genetic events inhibiting the intrinsic or extrinsic apoptotic pathways, as well as their modulators, such as the inhibitor of apoptosis proteins, P53, and components of the NF-kB pathway. Mechanisms of dysregulation include upregulation of anti-apoptotic proteins and downregulation of pro-apoptotic proteins via point mutations, amplifications, deletions, translocations, and influences of other proteins. Understanding the factors contributing to resistance to apoptosis in DLBCL is crucial in order to be able to develop targeted therapies that could improve outcomes by restoring apoptosis in malignant cells. This review describes the genetic events inhibiting apoptosis in DLBCL, provides a perspective of their interactions in lymphomagenesis, and discusses their implication for the future of DLBCL therapy.

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Targeting TRAIL

Cited by 9 publications

References 105 publications

Communication in the Cancer Microenvironment as a Target for Therapeutic Interventions

Communication in the Cancer Microenvironment as a Target for Therapeutic Interventions

Recent Advances in the Development of Nanodelivery Systems Targeting the TRAIL Death Receptor Pathway

Genetic Events Inhibiting Apoptosis in Diffuse Large B Cell Lymphoma

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