SMAC mimetics overcome apoptotic resistance in ovarian cancer through MSLN-TNF alpha axis Article Swipe
Ricardo Coelho
,
Brinton Seashore‐Ludlow
,
Sarah Schütz
,
Flavio C. Lombardo
,
Elisabeth Moussaud-Lamodière
,
Ruben Casanova
,
Joanna Ficek-Pascual
,
Kathrin B. Labrosse
,
Michal Hensler
,
Monica Lopez-Nunez
,
Natalie Rimmer
,
André Fedier
,
Renata de Lima
,
Céline Montavon
,
Christian Kurzeder
,
Franziska Singer
,
Anne Bertolini
,
Jitka Fučíková
,
Gunnar Rätsch
,
Bernd Bodenmiller
,
Olli Kallioniemi
,
Päivi Östling
,
Leonor David
,
Viola Heinzelmann‐Schwarz
,
Francis Jacob
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.01.24.576987
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.01.24.576987
Resistance to chemotherapy and PARPi inhibitors remains a critical challenge in the treatment of epithelial ovarian cancer, mainly due to disabled apoptotic responses in tumor cells. Given mesothelin’s pivotal role in ovarian cancer and its restricted expression in healthy tissues, we conducted a drug-screening discovery analysis across a range of genetically modified cancer cells to unveil mesothelin’s therapeutic impact. We observed enhanced cell death in cancer cells with low mesothelin expressing when exposed to a second mitochondria-derived activator of caspases (SMAC) mimetics, and demonstrated a compelling synergy when combined with chemotherapy in ex vivo patient-derived cultures and zebrafish tumor xenografts. Mechanistically, the addition of the SMAC mimetics drug birinapant to either carboplatin or paclitaxel triggered the activation of the Caspase 8-dependent apoptotic program facilitated by TNFα signaling. Multimodal analysis of neoadjuvant-treated patient samples further revealed an association between tumor-associated macrophages and the activation of TNFα-related pathways. Our proposed bimodal treatment shows promise in enhancing the clinical management of patients by harnessing the potential of SMAC mimetics alongside conventional chemotherapy.
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Concepts
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2024.01.24.576987
- https://www.biorxiv.org/content/biorxiv/early/2024/02/27/2024.01.24.576987.full.pdf
- OA Status
- green
- References
- 85
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4391270064
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4391270064Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/2024.01.24.576987Digital Object Identifier
- Title
-
SMAC mimetics overcome apoptotic resistance in ovarian cancer through MSLN-TNF alpha axisWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-01-26Full publication date if available
- Authors
-
Ricardo Coelho, Brinton Seashore‐Ludlow, Sarah Schütz, Flavio C. Lombardo, Elisabeth Moussaud-Lamodière, Ruben Casanova, Joanna Ficek-Pascual, Kathrin B. Labrosse, Michal Hensler, Monica Lopez-Nunez, Natalie Rimmer, André Fedier, Renata de Lima, Céline Montavon, Christian Kurzeder, Franziska Singer, Anne Bertolini, Jitka Fučíková, Gunnar Rätsch, Bernd Bodenmiller, Olli Kallioniemi, Päivi Östling, Leonor David, Viola Heinzelmann‐Schwarz, Francis JacobList of authors in order
- Landing page
-
https://doi.org/10.1101/2024.01.24.576987Publisher landing page
- PDF URL
-
https://www.biorxiv.org/content/biorxiv/early/2024/02/27/2024.01.24.576987.full.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.biorxiv.org/content/biorxiv/early/2024/02/27/2024.01.24.576987.full.pdfDirect OA link when available
- Concepts
-
Ovarian cancer, Carboplatin, Mesothelin, Cancer research, Paclitaxel, Apoptosis, Cancer, Chemotherapy, Medicine, Cancer cell, Biology, Cisplatin, Internal medicine, BiochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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85Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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