Targeting TRAIL in the treatment of cancer: new developments

Lim, Bora; Allen, Joshua E.; Prabhu, Varun V.; Talekar, Mala; Finnberg, Niklas; El‐Deiry, Wafik S.

doi:10.1517/14728222.2015.1049838

Cited by 91 publications

(68 citation statements)

References 85 publications

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“…There are several ongoing and completed clinical phase studies targeting TRAIL apoptotic pathway by using agents including monoclonal antibodies and recombinant human proteins, and these studies are giving promising results with no significant toxic effects [117].…”

Section: Fas Cell Surface Death Receptor and Fas Ligandmentioning

confidence: 99%

Major apoptotic mechanisms and genes involved in apoptosis

et al. 2016

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As much as the cellular viability is important for the living organisms, the elimination of unnecessary or damaged cells has the opposite necessity for the maintenance of homeostasis in tissues, organs and the whole organism. Apoptosis, a type of cell death mechanism, is controlled by the interactions between several molecules and responsible for the elimination of unwanted cells from the body. Apoptosis can be triggered by intrinsically or extrinsically through death signals from the outside of the cell. Any abnormality in apoptosis process can cause various types of diseases from cancer to auto-immune diseases. Different gene families such as caspases, inhibitor of apoptosis proteins, B cell lymphoma (Bcl)-2 family of genes, tumor necrosis factor (TNF) receptor gene superfamily, or p53 gene are involved and/or collaborate in the process of apoptosis. In this review, we discuss the basic features of apoptosis and have focused on the gene families playing critical roles, activation/inactivation mechanisms, upstream/downstream effectors, and signaling pathways in apoptosis on the basis of cancer studies. In addition, novel apoptotic players such as miRNAs and sphingolipid family members in various kind of cancer are discussed.

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Section: Fas Cell Surface Death Receptor and Fas Ligandmentioning

confidence: 99%

Major apoptotic mechanisms and genes involved in apoptosis

et al. 2016

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“…This could be of particular interest, as TRAIL shows a selective and promising antitumor action in different tumor cells (B. Lim, et al, 2015;Mitsiades, et al, 2001;Yagita, et al, 2004). Several reports have shown an increase in the cytotoxic activity of edelfosine when combined with additional antitumor drugs, such as: a) vincristine in human glioma cells (Haugland, et al, 1999); b) merocyanine 540 in human neuroblastoma, osteosarcoma, Wilms' tumor, leukemia, breast cancer cells, as well as murine neuroblastoma and breast cancer cells (Anderson, et al, 2002;Anderson, et al, 2003;Yamazaki & Sieber, 1997); and c) gemcitabine with clofarabine in human T cell-lymphoma cells (Valdez, et al, 2014).…”

Section: Edelfosinementioning

confidence: 99%

Alkyl ether lipids, ion channels and lipid raft reorganization in cancer therapy

Jaffrès

Gajate

Bouchet

et al. 2016

Pharmacology & Therapeutics

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Synthetic alkyl lipids, such as the ether lipids edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) and ohmline (1-O-hexadecyl-2-O-methyl-rac-glycero-3-β-lactose), are forming a class of antitumor agents that target cell membranes to induce apoptosis and to decrease cell migration/invasion, leading to the inhibition of tumor and metastasis development. In this review, we present the structure-activity relationship of edelfosine and ohmline, and we point out differences and similarities between these two amphiphilic compounds. We also discuss the mechanisms of action of these synthetic alkyl ether lipids (involving, among other structures and molecules, membrane domains, Fas/CD95 death receptor signaling, and ion channels), and highlight a key role for lipid rafts in the underlying process. The reorganization of lipid raft membrane domains induced by these alkyl lipids affects the function of death receptors and ion channels, thus leading to apoptosis and/or inhibition of cancer cell migration. The possible therapeutic use of these alkyl lipids and the clinical perspectives for these lipids in prevention or/and treatment of tumor development and metastasis are also discussed.

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“…Binding of TRAIL to death receptors, DR4 and/or DR5, triggers the caspase-dependent extrinsic apoptosis pathway, which also cooperates with the intrinsic apoptosis pathway mediated by mitochondria. 4 To exploit the tumor killing ability of TRAIL in therapy, different recombinant forms of human TRAIL or DR4/DR5 agonist antibodies have been developed and are being tested. 4,5 Although TRAIL has the ability to selectively kill cancer cells, 3 many cancer cells are intrinsically resistant or acquire resistance to TRAIL.…”

Section: Introductionmentioning

confidence: 99%

“…4 To exploit the tumor killing ability of TRAIL in therapy, different recombinant forms of human TRAIL or DR4/DR5 agonist antibodies have been developed and are being tested. 4,5 Although TRAIL has the ability to selectively kill cancer cells, 3 many cancer cells are intrinsically resistant or acquire resistance to TRAIL. While the mechanisms behind TRAIL resistance are still ill-defined, they include aberrant expression or dysregulation of apoptosis pathway components at the transcriptional level, such as the suppression of death receptors 6 or at the protein level, such as the degradation of FLIP.…”

Section: Introductionmentioning

confidence: 99%

Identification of Mitoxantrone as a TRAIL-sensitizing agent for Glioblastoma Multiforme

Senbabaoglu

Cingöz

Kaya

et al. 2016

Cancer Biology & Therapy

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Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) has tremendous promise in treating various forms of cancers. However, many cancer cells exhibit or develop resistance to TRAIL. Interestingly, many studies have identified several secondary agents that can overcome TRAIL resistance. To expand on these studies, we conducted an extensive drug-re-profiling screen to identify FDA-approved compounds that can be used clinically as TRAIL-sensitizing agents in a very malignant type of brain cancer, Glioblastoma Multiforme (GBM). Using selected isogenic GBM cell pairs with differential levels of TRAIL sensitivity, we revealed 26 TRAIL-sensitizing compounds, 13 of which were effective as single agents. Cardiac glycosides constituted a large group of TRAIL-sensitizing compounds, and they were also effective on GBM cells as single agents. We then explored a second class of TRAIL-sensitizing drugs, which were enhancers of TRAIL response without any effect on their own. One such drug, Mitoxantrone, a DNAdamaging agent, did not cause toxicity to non-malignant cells at the doses that synergized with TRAIL on tumor cells. We investigated the downstream changes in apoptosis pathway components upon Mitoxantrone treatment, and observed that Death Receptors (DR4 and DR5) expression was upregulated, and pro-apoptotic and anti-apoptotic gene expression patterns were altered in favor of apoptosis. Together, our results suggest that combination of Mitoxantrone and TRAIL can be a promising therapeutic approach for GBM patients.

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Targeting TRAIL in the treatment of cancer: new developments

Cited by 91 publications

References 85 publications

Major apoptotic mechanisms and genes involved in apoptosis

Major apoptotic mechanisms and genes involved in apoptosis

Alkyl ether lipids, ion channels and lipid raft reorganization in cancer therapy

Identification of Mitoxantrone as a TRAIL-sensitizing agent for Glioblastoma Multiforme

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