Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : Oncothyreon -- Ignore unavailable to you. Want to Upgrade?

To: biomachine56 who wrote (2184)	5/30/2013 12:28:13 AM
From: biomachine56	Read Replies (1) \| Respond to of 2344

Head and Neck cancer ncbi.nlm.nih.gov 1.2. Squamous cell carcinoma of the head and neck (SCCHN) as a unique EGFR-dependent cancer Several lines of evidence have pointed to EGFR as an important therapeutic target in SCCHN. EGFR expression is elevated relative to expression on normal adjacent squamous mucosa in over 80% of invasive head and neck cancers ( Figure 3.I) [The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version. Destroy user interface control 16]. Depletion of antibody-bound EGFR from the cell surface may be the most important underlying mechanism of cetuximab activity in vivo [The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version. Destroy user interface control 37], and, interestingly, SCCHN cell lines selected for cetuximab resistance have often acquired an endocytosis deficiency [The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version. Destroy user interface control 38]. Cetuximab monotherapy in patients with recurrent/metastatic SCCHN who had progressed on platinum-based chemotherapy resulted in an objective response rate of 13% [50]. Monotherapy response rates have been 10% or less for aminoquinazolines, with no survival benefit with gefitinib when compared to second line conventional chemotherapy The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version. Destroy user interface controlAlthough the activity of EGFR inhibitors in SCCHN patients is clear, clinical results are modest. This suggests that majority of patients are either refractory from the commencement of treatment, or rapidly acquire resistance. 2.3 Resistance mechanisms originating from EGFR downstream effectors Many studies have documented changes in this protein network as contributing to resistance to EGFR. The most important sources of resistance in SCCHN are outlined below. 2.3.1. PI3K / AKT / PTEN Deregulation of the PI3K/AKT pathway is associated with resistance to EGFR inhibitors. 3.1. EGFR inhibitors and STAT or SRC inhibitorsAlthough STATs have attracted interest as therapeutic targets, these efforts are still at an early stage Although no STAT inhibitor has been tested in the clinic for SCCHN, STAT3 has attracted interest as a therapeutic target in SCCHN, particularly with the idea the combination of EGFR-inhibition with a STAT inhibitor would be a prductive therapeutic strategy. 3.3. EGFR inhibitors and mTOR inhibitorsBlockade of the mammalian target of rapamycin (mTOR) is under investigation in SCCHN. Targeting mTOR prevents activation of the essential resistance and growth signals emanating from PI3K and Akt and increases potency of the EGFR antagonists in resistant cancer cell lines. The signal transduction pathway involving PI3K/Akt and mTOR is associated with cellular nutrient regulation and proliferation and has been implicated in the regulation of angiogenesis via the increased activity of hypoxia inducible factor -1 alpha (HIF-1a) and VEGF [223-225].Jimeno et al. demonstrated synergistic antitumor effects of temsirolimus and erlotinib in resistant SCCHN cell line which were also paralleled by downregulation of MAPK, S6p70 phosphorylation and suppression of proliferation. The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version. Destroy user interface control