IndraLab

Statements

Sunitinib inhibits CTSB. 4 / 4
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"Indeed, pazopanib was shown to induce cathepsin-B activation and cell death by autophagy while sunitinib was shown to impair cathepsin-B activation and stimulate lysosomaldependent necrosis, suggesting a rationale for sequential use of these, and possibly other, tyrosine kinase inhibitors [68].4.3.2 Pazopanib in Phase II trials 4.3.2.1 Pazopanib as a first-line therapy in patients with metastatic urothelial carcinoma A Phase II trial is currently ongoing investigating the use of pazopanib in association with cisplatin in patients with advanced solid tumors including metastatic bladder cancer [69]."
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"In 786-O cells, sunitinib accumulated in lysosomes and disrupted autophagic degradation by inhibiting the activity of the lysosomal protease cathepsin B, which promotes to sunitinib resistance of ccRCC ."
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"We found that sunitinib treatment for 24h triggers incomplete autophagy, impairs cathepsin B activation and stimulates a lysosomal dependent necrosis."
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"Sunitinib accumulates continuously in lysosomes, inhibiting CTSB activity and resulting in incomplete autophagic flux."
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