کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5525580 | 1546673 | 2017 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Mini-reviewCo-targeting of EGFR and autophagy signaling is an emerging treatment strategy in metastatic colorectal cancer Mini-reviewCo-targeting of EGFR and autophagy signaling is an emerging treatment strategy in metastatic colorectal cancer](/preview/png/5525580.png)
- Molecular mechanisms of resistance to anti-EGFR antibodies.
- Acquired resistance accompanied by inhibition of EGFR internalization and sorting.
- Anti-EGFR MoAbs can promote autophagy.
- Targeting autophagy machinery inhibit EGFR trafficking - New therapeutic strategy.
The epidermal growth factor receptor (EGFR) and its associated pathway is a critical key regulator of CRC development and progression. The monoclonal antibodies (MoAbs) cetuximab and panitumumab, directed against EGFR, represent a major step forward in the treatment of metastatic colorectal cancer (mCRC), in terms of progression-free survival and overall survival in several clinical trials. However, the activity of anti-EGFR MoAbs appears to be limited to a subset of patients with mCRC. Studies have highlighted that acquired-resistance to anti-EGFR MoAbs biochemically converge into Ras/Raf/Mek/Erk and PI3K/Akt/mTOR pathways. Recent data also suggest that acquired-resistance to anti-EGFR MoAbs is accompanied by inhibition of EGFR internalization, ubiqutinization, degradation and prolonged downregulation. It is well established that autophagy, a self-cannibalization process, is considered to be associated with resistance to the anti-EGFR MoAbs therapy. Additionally, autophagy induced by anti-EGFR MoAbs acts as a protective response in cancer cells. Thus, inhibition of autophagy after treatment with EGFR MoAbs can result in autophagic cell death. A combination therapy comprising of anti-EGFR MoAbs and autophagy inhibitors would represent a multi-pronged approach that could be evolved into an active therapeutic strategy in mCRC patients.
Journal: Cancer Letters - Volume 396, 28 June 2017, Pages 94-102