Death receptors as targets in cancer

Micheau, Olivier; Shirley, Sarah; Dufour, Florent

doi:10.1111/bph.12238

Cited by 175 publications

(169 citation statements)

References 172 publications

(218 reference statements)

Supporting

Mentioning

168

Contrasting

Unclassified

Order By: Relevance

“…We provide thus a proof-of-concept that TRAIL nanovector derivatives based on SWCNT may be useful to future nanomedicine therapies. 6,7 In this context, current therapeutic approaches aim at combining TRAIL with conventional chemotherapy or targeted therapies to circumvent different resistances to TRAIL-induced apoptosis due to the presence of the antagonist receptors TRAIL-R3 (DcR1) and TRAIL-R4 (DcR2),the caspase-8 inhibitor c-FLIPor to a defect in the mitochondrial pathway. [8][9][10] Alternatively, mutagenesisor multimerization of TRAIL (or TRAIL derivatives)to mimic native membrane-bound TRAIL are explored to increase TRAIL efficacy.…”

mentioning

confidence: 99%

Nanovectorization of TRAIL with Single Wall Carbon Nanotubes Enhances Tumor Cell Killing

et al. 2015

View full text Add to dashboard Cite

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) is a member of the tumor necrosis factor (TNF) superfamily. This type II transmembrane protein is able to bound specifically to cancer cell receptors (i.e., TRAIL-R1 (or DR4) and TRAIL-R2 (or DR5)) and to induce apoptosis without being toxic for healthy cells. Because membrane-bound TRAIL induces stronger receptor aggregation and apoptosis than soluble TRAIL, we proposed here to vectorize TRAIL using single-walled carbon nanotubes (SWCNTs) to mimic membrane TRAIL. Owing to their exceptional and revolutional properties, carbon nanotubes, especially SWCNTs, are used in a wide range of physical or, now, medical applications. Indeed due to their high mechanical resistance, their high flexibility and their hydrophobicity, SWCNTs are known to rapidly diffuse in an aqueous medium such as blood, opening the way of development of new drug nanovectors (or nanocarriers). Our TRAIL-based SWCNTs nanovectors proved to be more efficient than TRAIL alone death receptors in triggering cancer cell killing. These NPTs increased TRAIL pro-apoptotic potential by nearly 20-fold in different Human tumor cell lines including colorectal, nonsmall cell lung cancer, or hepatocarcinomas. We provide thus a proof-of-concept that TRAIL nanovector derivatives based on SWCNT may be useful to future nanomedicine therapies.

show abstract

mentioning

confidence: 99%

Nanovectorization of TRAIL with Single Wall Carbon Nanotubes Enhances Tumor Cell Killing

et al. 2015

View full text Add to dashboard Cite

show abstract

“…One of the mechanisms by which tumors evade apoptosis is by overexpression of antiapoptotic proteins such as the caspase-8 inhibitor FLIP, which blocks induction of apoptosis mediated by death receptors such as Fas, DR4 (TRAIL-R1) and DR5 (TRAIL-R2) (7,8). FLIP inhibits homo-dimerization, self-processing and activation of procaspase-8 at the deathinducing signalling complexes (DISCs) formed following activation of these receptors.…”

Section: Introductionmentioning

confidence: 99%

FLIP: A Targetable Mediator of Resistance to Radiation in Non–Small Cell Lung Cancer

McLaughlin

Németh

Bradley

et al. 2016

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Resistance to radiotherapy due to insufficient cancer cell death is a significant cause of treatment failure in non-small cell lung cancer (NSCLC). The endogenous caspase-8 inhibitor, FLIP, is a critical regulator of cell death that is frequently overexpressed in NSCLC and is an established inhibitor of apoptotic cell death induced via the extrinsic death receptor pathway. Apoptosis induced by ionizing radiation (IR) has been considered to be mediated predominantly via the intrinsic apoptotic pathway; however, we found that IR-induced apoptosis was significantly attenuated in NSCLC cells when caspase-8 was depleted using RNA interference (RNAi), suggesting involvement of the extrinsic apoptosis pathway.Moreover, overexpression of wild-type FLIP, but not a mutant form that cannot bind the critical death receptor adaptor protein FADD, also attenuated IR-induced apoptosis, confirming the importance of the extrinsic apoptotic pathway as a determinant of response to IR in NSCLC. Importantly, when FLIP protein levels were down-regulated by RNAi, IRinduced cell death was significantly enhanced. The clinically relevant histone deacetylase (HDAC) inhibitors vorinostat and entinostat were subsequently found to sensitize a subset of NSCLC cell lines to IR in a manner that was dependent on their ability to suppress FLIP expression and promote activation of caspase-8. Entinostat also enhanced the anti-tumor activity of IR in vivo. Therefore, FLIP down-regulation induced by HDAC inhibitors is a potential clinical strategy to radio-sensitize NSCLC and thereby improve response to radiotherapy. Overall, this study provides the first evidence that pharmacological inhibition of FLIP may improve response of NCSLC to IR. KA McLaughlin et al. FLIP-mediated radio-resistance in NSCLC3

show abstract

“…However, since some cancer cells respond poorly to recombinant TRAIL formulations currently available, novel TRAIL versions with increased bioactivity would be potentially useful [9,10].…”

Section: Introductionmentioning

confidence: 99%

Liposome-bound TRAIL induces superior DR5 clustering and enhanced DISC recruitment in histiocytic lymphoma U937 cells

et al. 2015

View full text Add to dashboard Cite

Death receptors as targets in cancer

Cited by 175 publications

References 172 publications

Nanovectorization of TRAIL with Single Wall Carbon Nanotubes Enhances Tumor Cell Killing

Nanovectorization of TRAIL with Single Wall Carbon Nanotubes Enhances Tumor Cell Killing

FLIP: A Targetable Mediator of Resistance to Radiation in Non–Small Cell Lung Cancer

Liposome-bound TRAIL induces superior DR5 clustering and enhanced DISC recruitment in histiocytic lymphoma U937 cells

Contact Info

Product

Resources

About