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- W2019708706 abstract "Notch signaling plays an important role in development and cell fate determination, and it is deregulated in human hematologic malignancies and solid tumors. This review includes a brief introduction of the relevant pathophysiology of Notch signaling pathway and primarily focuses on the clinical development of promising agents that either obstruct Notch receptor cleavages such as γ-secretase inhibitors (GSIs) or interfere with the Notch ligand–receptor interaction by monoclonal antibodies (mAbs). Antitumor activity by GSIs and mAbs administered as single agent in early phases of clinical trials has been observed in advanced or metastatic thyroid cancer, non-small cell lung cancer, intracranial tumors, sarcoma or desmoid tumors, colorectal cancer with neuroendocrine features, melanoma and ovarian cancer. A number of mechanism-based adverse events particularly gastrointestinal toxicities emerged and mitigation strategies are developed after testing multiple GSIs and Notch targeting mAbs. We also discuss pharmacodynamic biomarkers in conjunction with methods of assessment of the molecular target inhibition validation. Biomarkers of efficacy or benefit may be of importance for a successful development of this class of drugs." @default.
- W2019708706 created "2016-06-24" @default.
- W2019708706 creator A5003596801 @default.
- W2019708706 creator A5047689869 @default.
- W2019708706 creator A5082874698 @default.
- W2019708706 date "2014-02-01" @default.
- W2019708706 modified "2023-10-14" @default.
- W2019708706 title "Targeting Notch signaling pathway in cancer: Clinical development advances and challenges" @default.
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