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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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Langdon, Simon P.
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article
Evaluation of carbonic anhydrase IX as a therapeutic target for inhibition of breast cancer invasion and metastasis using a series of in vitro breast cancer models
Abstract
<p>Triplenegative,resistantormetastaticdiseasearemajorfactorsinbreastcancer mortality, warranting novel approaches. Carbonic anhydrase IX (CAIX) is implicated in survival, migration and invasion of breast cancer cells and inhibition provides an innovative therapeutic strategy. The efficacy of 5 novel ureido-substituted sulfamate CAIXinhibitorswereassessedinincreasinglycomplexbreastcancermodels, including cell lines in normoxia and hypoxia, 3D spheroids and an <em>ex-vivo</em> explant modelutilizingfreshbiopsytissuefromdifferentbreastcancersubtypes.CAIXexpression was evaluated in a tissue microarray (TMA) of 92 paired lymph node and primary breast cancers and 2 inhibitors were appraised <em>in vivo</em>using MDA-MB-231 xenografts.FC11409B,FC9398A,FC9403,FC9396AandS4decreasedcell proliferation and migration and inhibited 3D spheroid invasion. S4, FC9398A and FC9403Ainhibitedorpreventedinvasionintocollagen.FC9403A significantly reversedestablishedinvasionwhilstFC9398AandDTP348reducedxenograft growth. TMA analysis showed increased CAIX expression in triplenegative cancers.These data establish CAIX inhibition as a relevant therapeutic goal in breast cancer, targeting the migratory, invasive, and metastatic potential of this disease. The use of biopsy tissue suggests efficacy against breast cancer subtypes,and should provide a useful tool in drug testing against invasive cancers.</p>