Track topics on Twitter Track topics that are important to you
Important steps in embryonic development are governed by the Hedgehog (Hh) signaling pathway, an evolutionary conserved signal transduction cascade. However, Hh activity is not only crucial during embryo formation, but is also involved in adult tissue repair and in several malignancies. Particularly due to its link to cancer, small molecule Hh pathway inhibitors have been developed and the first compounds have been approved for use in Hh-driven basal cell carcinoma. Almost all advanced Hh inhibitors target the critical signaling component Smoothened (SMO), but pre-clinical research has identified additional compounds which can block the Hh pathway along its entire signaling cascade, which, in light of emerging drug resistance occurring with SMO inhibitors, is of high importance. Herein we give an overview on currently known Hh pathway inhibitors, delineating their respective strengths and weaknesses and describing potential drug targeting strategies to interfere with Hh signaling in different cancer settings.
This article was published in the following journal.
Name: Journal of medicinal chemistry
Primary cilia are required for Smoothened to transduce vertebrate Hedgehog signals, but how Smoothened accumulates in cilia and is activated is incompletely understood. Here, we identify cilia-associa...
To investigate export of Hedgehog pathway (Hh) proteins Patched1, Smoothened, Sonic hedgehog and Indian hedgehog in cervical cancer cell line (CaCx) exosomes.
The hedgehog pathway, for which sonic hedgehog (Shh) is the most prominent ligand, is highly conserved and is tightly associated with embryonic development in a number of species. This pathway is also...
Wnt pathway is an evolutionarily conserved signaling pathway determining patterning of animal embryos, cell fate, cell polarity, and a substantial role in the origin and maintenance of stem cells. It ...
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...
This clinical trial is looking at the effect of a new drug called GDC-0449 in patients with cancer of the pancreas. Laboratory studies have shown that this drug blocks a process in pancrea...
The present study on pharmacological intervention in autonomic nervous dysregulation(parasympathetic dysfunction,) regarding insulin resistance, is a concept testing in humans tohelp ident...
This is an open-label, single arm, multi-center, Phase II trial to evaluate the progression free survival in patients with metastatic adenocarcinoma of the pancreas treated with a hedgehog...
The purpose of this study is to update the EORTC QLQ Breast (BR)-23 Module. Since the development of BR-23 published 1996 the standard therapy of breast cancer has changed. New therapies b...
A frizzled-like, G-protein-coupled receptor that associates with PATCHED RECEPTORS to transduce signals from HEDGEHOG PROTEINS and initiate hedgehog signaling to ZINC FINGER PROTEIN GLI1. It may normally inhibit signaling in the absence of SONIC HEDGEHOG PROTEIN binding to PATCHED RECEPTOR-1.
A family of intercellular signaling proteins that play and important role in regulating the development of many TISSUES and organs. Their name derives from the observation of a hedgehog-like appearance in DROSOPHILA embryos with genetic mutations that block their action.
Systems for the delivery of drugs to target sites of pharmacological actions. Technologies employed include those concerning drug preparation, route of administration, site targeting, metabolism, and toxicity.
A patched receptor for several HEDGEHOG PROTEINS that associates with the SMOOTHENED RECEPTOR to modulate hedgehog signaling. It is also a TUMOR SUPPRESSOR PROTEIN; mutations in the patched-1 gene are associated with BASAL CELL NEVUS SYNDROME; SQUAMOUS CELL CARCNIOMA of the ESOPHAGUS; trichoepitheliomas, and CARCINOMA, TRANSITIONAL CELL of the URINARY BLADDER.
A cytoplasmic receptor and peroxin that contains a series of TETRACOTIPEPTIDE REPEATS and binds to PEROXISOME TARGETING SIGNAL 1 (SKL-type). It is essential for protein import into PEROXISOMES; mutations in the PEX5 gene are associated with PEROXISOMAL DISORDERS such as ZELLWEGER SYNDROME.
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...
There are three main types of skin cancer: basal cell carcinoma, squamous cell carcinoma and malignant melanoma. Basal cell carcinoma Basal cell carcinoma, or BCC, is a cancer of the basal cells at the bottom of the epidermis. It’s very common ...
Clinical Research Organization
Contract Research Organization (CRO) provide research services outsourced on a contract basis to the pharmaceutical, biotechnology, healthcare and medical device industries: biopharmaceutical development biologic assay development commercial...