The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.
Mammalian target of rapamycin, a molecular target in squamous cell carcinomas of the head and neck.
Panomwat Amornphimoltham; Vyomesh Patel; Akrit Sodhi; Nikolaos G Nikitakis; John J Sauk; Edward A Sausville; Alfredo A Molinolo; J Silvio Gutkind (Profiled Author: Akrit Sodhi)
Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda 20892-4330, USA.
Cancer research 2005;65(21):9953-61.
Emerging knowledge on how the dysregulated function of signaling networks contributes to the malignant growth of squamous cell carcinoma of the head and neck (HNSCC) can now be exploited to identify novel mechanism-based anticancer treatments. In this regard, we have observed that persistent activation of the serine/threonine kinase Akt is a frequent event in HNSCC, and that blockade of its upstream kinase, 3'-phosphoinositide-dependent kinase 1, potently inhibits tumor cell growth. Akt promotes cell proliferation by its ability to coordinate mitogenic signaling with energy- and nutrient-sensing pathways that control protein synthesis through the atypical serine/threonine kinase, mammalian target of rapamycin (mTOR). This kinase, in turn, phosphorylates key eukaryotic translation regulators, including p70-S6 kinase and the eukaryotic translation initiation factor, 4E binding protein 1. Indeed, we show here that aberrant accumulation of the phosphorylated active form of S6, the most downstream target of the Akt-mTOR-p70-S6 kinase pathway, is a frequent event in clinical specimens from patients with HNSCC and their derived cell lines. Of interest, this enhanced level of the phosphorylated active form of S6 was rapidly reduced in HNSCC cell lines and HNSCC xenograft models at clinically relevant doses of rapamycin, which specifically inhibits mTOR. Furthermore, we observed that rapamycin displays a potent antitumor effect in vivo, as it inhibits DNA synthesis and induces the apoptotic death of HNSCC cells, ultimately resulting in tumor regression. These findings identify the Akt-mTOR pathway as a potential therapeutic target for HNSCC, and may provide the rationale for the early clinical evaluation of rapamycin and its analogues in patients with HNSCC.
This section shows information related to the publication - computed using the fingerprint of the publication - including related publications, related experts and related grants with fingerprints representing significant amounts of overlap between their fingerprint and this publication. The red dots indicate whether those experts or terms appear within the publication, thereby showing potential and actual connections.
Wen Wee Ma; Heather Jacene; Dongweon Song; Felip Vilardell; Wells A Messersmith; Dan Laheru; Richard Wahl; Chris Endres; Antonio Jimeno; Martin G Pomper; et al.Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2009;27(16):2697-704.
A Jimeno; P Kulesza; J Wheelhouse; A Chan; X Zhang; E Kincaid; R Chen; D P Clark; A Forastiere; M HidalgoBritish journal of cancer 2007;96(6):952-9.
Linda A deGraffenried; William E Friedrichs; Douglas H Russell; Elissa J Donzis; Amanda K Middleton; Jessica M Silva; Richard A Roth; Manuel HidalgoClinical cancer research : an official journal of the American Association for Cancer Research 2004;10(23):8059-67.
Appears in this Publication
Author of this Publication