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The Notch signaling pathway, which is highly conserved from sea urchins to humans, plays an important role in cell-differentiation, survival, proliferation, stem-cell renewal, and determining cell fate during development and morphogenesis. It is well established that signaling pathways are dysregulated in a wide-range of diseases, including human malignancies. Studies suggest that the dysregulation of the Notch pathway contributes to carcinogenesis, cancer stem cell renewal, angiogenesis, and chemo-resistance. Elevated levels of Notch receptors and ligands have been associated with cancer-progression and poor survival. Furthermore, the Notch signaling pathway regulates the transcriptional activity of key target genes through crosstalk with several other signaling pathways. Indeed, increasing evidence suggests that the Notch signaling pathway may serve as a therapeutic target for the treatment of several cancers, including breast cancer. Researchers have demonstrated the anti-tumor properties of Notch inhibitors in various cancer types. Currently, Notch inhibitors are being evaluated for anticancer efficacy in a number of clinical-trials. However, because there are multiple Notch receptors that can exhibit either oncogenic or tumor-suppressing roles in various cells, it is important that the Notch inhibitors are specific to particular receptors that are tumorigenic in nature. This review critically evaluates existing Notch inhibitory drugs and strategies and summarizes the previous discoveries, current understandings, and recent developments in support of Notch receptors as therapeutic targets in breast cancer.
This article was published in the following journal.
Name: Cancer letters
During CD8+ T cell response, Notch signaling controls short-lived-effector-cell (SLEC) generation, but the exact mechanisms by which it does so remains unclear. The Notch signaling pathway can act as ...
Radiation therapy is the primary treatment for primary nasopharyngeal carcinoma (NPC). The aim of this study is to identify the effect of the Numb/Notch signaling pathway on radiation sensitivity in h...
Coordinated migration of cell collectives is important during embryonic development and relies on cells integrating multiple mechanical and chemical cues. Recently, we described that focal activation ...
DNER, Delta/Notch-like epidermal growth factor (EGF)-related receptor, is a neuron-specific transmembrane protein carrying extracellular EGF-like repeats. The function of DNER in breast cancer has not...
Breast cancer is a common malignancy that is highly lethal with poor survival rates and immature therapeutics that urgently needs more effective and efficient therapies. MicroRNAs are intrinsically in...
An investigational study to determine the safety/tolerability, and efficacy of a notch signaling pathway inhibitor in patients with metastatic or locally advanced breast cancer and other a...
This randomized phase I/II clinical trial is studying the side effects and best dose of gamma-secretase/notch signalling pathway inhibitor RO4929097 when given together with vismodegib and...
The purpose of this study is to demonstrate that orally administered itraconazole, a commonly used antifungal medication, can inhibit Hedgehog pathway signaling in patients with esophageal...
The purpose of this study is to determine the feasibility of a short term administration of a targeted therapy (i.e., anastrozole) in women with newly diagnosed early invasive or non invas...
This phase Ib/II trial studies the side effects and best dose of gamma-secretase/Notch signalling pathway inhibitor RO4929097 when given together with cisplatin, vinblastine, and temozolom...
Abnormal accumulation of lymph in the arm, shoulder and breast area associated with surgical or radiation breast cancer treatments (e.g., MASTECTOMY).
Metastatic breast cancer characterized by EDEMA and ERYTHEMA of the affected breast due to LYMPHATIC METASTASIS and eventual obstruction of LYMPHATIC VESSELS by the cancer cells.
A complex signaling pathway whose name is derived from the DROSOPHILA Wg gene, which when mutated results in the wingless phenotype, and the vertebrate INT gene, which is located near integration sites of MOUSE MAMMARY TUMOR VIRUS. The signaling pathway is initiated by the binding of WNT PROTEINS to cells surface WNT RECEPTORS which interact with the AXIN SIGNALING COMPLEX and an array of second messengers that influence the actions of BETA CATENIN.
A disintegrin and metalloproteinase domain-containing protein that cleaves the membrane-bound precursor of TUMOR NECROSIS FACTOR-ALPHA to its mature form. It cleaves several other CELL SURFACE PROTEINS, including INTERLEUKIN-1 RECEPTOR TYPE II; TRANSFORMING GROWTH FACTOR ALPHA; L-SELECTIN; MUCIN-1; and AMYLOID BETA-PROTEIN PRECURSOR. It can also function as an activator of the Notch signaling pathway by mediating the cleavage of NOTCH RECEPTORS.
A infiltrating (invasive) breast cancer, relatively uncommon, accounting for only 5%-10% of breast tumors in most series. It is often an area of ill-defined thickening in the breast, in contrast to the dominant lump characteristic of ductal carcinoma. It is typically composed of small cells in a linear arrangement with a tendency to grow around ducts and lobules. There is likelihood of axillary nodal involvement with metastasis to meningeal and serosal surfaces. (DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1205)
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Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...