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| Naji, M. |
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| Motta, Antonella |
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| Aletan, Dirar |
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| Mohamed, Tarek |
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| Ertürk, Emre |
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| Taccardi, Nicola |
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| Kononenko, Denys |
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| Petrov, R. H. | Madrid |
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| Alshaaer, Mazen | Brussels |
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| Bih, L. |
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| Casati, R. |
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| Muller, Hermance |
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| Kočí, Jan | Prague |
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| Šuljagić, Marija |
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| Kalteremidou, Kalliopi-Artemi | Brussels |
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| Azam, Siraj |
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| Ospanova, Alyiya |
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| Blanpain, Bart |
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| Ali, M. A. |
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| Popa, V. |
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| Rančić, M. |
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| Ollier, Nadège |
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| Azevedo, Nuno Monteiro |
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| Landes, Michael |
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| Rignanese, Gian-Marco |
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Salomon, A.
in Cooperation with on an Cooperation-Score of 37%
Topics
Publications (14/14 displayed)
- 2021Formation of Interface Layers between Corundum-Based Refractory Ceramics with Carbon Additions and Molten 42CrMo4 Steelcitations
- 2020BRCAness, SLFN11, and RB1 loss predict response to topoisomerase I inhibitors in triple-negative breast cancers.citations
- 2018Heteroepitaxial growth of passivating layers on rutile in contact with molten aluminium and molten A356 aluminium alloy
- 2017Formation of different alumina phases and magnesium aluminate spinel during contact of molten AlSi7Mg0.6 alloy with mullite and amorphous silicacitations
- 2017Thermally Induced Formation of Transition Aluminas from Boehmitecitations
- 2017Functionalized Carbon-Bonded Filters with an Open Porous Alumina Coating: Impact of Time on Interactions and Steel Cleanlinesscitations
- 2017Formation of Corundum, Magnesium Titanate, and Titanium(III) Oxide at the Interface between Rutile and Molten Al or AlSi7Mg0.6 Alloycitations
- 2015Temperature evolution of microstructure of turbostratic high melting coal-tar synthetic pitch studied using wide-angle X-ray scattering methodcitations
- 2015Reaction mechanism between the carbon bonded magnesia coatings deposited on carbon bonded alumina and a steel melt
- 2014Reaction mechanism between the carbon bonded magnesia coatings deposited on carbon bonded alumina and a steel meltcitations
- 2013Dynamic, in situ generated interfaces between carbon-bonded alumina filters and steel during spark plasma sintering/field-assisted sinteringcitations
- 2013Comparison of interfacial reactions between AlSi7Mg and alumina filter after casting and spark plasma sinteringcitations
- 2013Simulations of X-ray scattering on two-dimensional, graphitic and turbostratic carbon structurescitations
- 2012Field assisted sintering technique compaction of ultrafine-Grained binderless WC Hard Metalscitations
Places of action
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article
BRCAness, SLFN11, and RB1 loss predict response to topoisomerase I inhibitors in triple-negative breast cancers.
Abstract
Topoisomerase I (TOP1) inhibitors trap TOP1 cleavage complexes resulting in DNA double-strand breaks (DSBs) during replication, which are repaired by homologous recombination (HR). Triple-negative breast cancer (TNBC) could be eligible for TOP1 inhibitors given the considerable proportion of tumors with a defect in HR-mediated repair (BRCAness). The TOP1 inhibitor irinotecan was tested in 40 patient-derived xenografts (PDXs) of TNBC. BRCAness was determined with a single-nucleotide polymorphism (SNP) assay, and expression of Schlafen family member 11 (SLFN11) and retinoblastoma transcriptional corepressor 1 (RB1) was evaluated by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry analyses. In addition, the combination of irinotecan and the ataxia telangiectasia and Rad3-related protein (ATR) inhibitor VE-822 was tested in SLFN11-negative PDXs, and two clinical non-camptothecin TOP1 inhibitors (LMP400 and LMP776) were tested. Thirty-eight percent of the TNBC models responded to irinotecan. BRCAness combined with high SLFN11 expression and RB1 loss identified highly sensitive tumors, consistent with the notion that deficiencies in cell cycle checkpoints and DNA repair result in high sensitivity to TOP1 inhibitors. Treatment by the ATR inhibitor VE-822 increased sensitivity to irinotecan in SLFN11-negative PDXs and abolished irinotecan-induced phosphorylation of checkpoint kinase 1 (CHK1). LMP400 (indotecan) and LMP776 (indimitecan) showed high antitumor activity in BRCA1-mutated or BRCAness-positive PDXs. Last, low SLFN11 expression was associated with poor survival in 250 patients with TNBC treated with anthracycline-based chemotherapy. In conclusion, a substantial proportion of TNBC respond to irinotecan. BRCAness, high SLFN11 expression, and RB1 loss are highly predictive of response to irinotecan and the clinical indenoisoquinoline TOP1 inhibitors.