ErbB antagonists patenting: Playing chess with cancer""

被引：10

作者：

Aifa, Sami ^{[1
]}

Rebai, Ahmed ^{[1
]}

机构：

[1] Unit of Bioinformatics and Signalling, Centre of Biotechnology of Sfax, Sfax

来源：

Recent Patents on Biotechnology | 2008年 / 2卷 / 03期

关键词：

EGFR; ErbB; MAb; Resistance mutations; Therapy; TKI;

D O I：

10.2174/187220808786240980

中图分类号：

学科分类号：

摘要：

ErbBs signalling is always associated with the development of the majority of solid cancers via both the MAPK pathway leading to cell cycle progression and the PI3K pathway causing cell survival. As a consequence, many ErbB antagonists have been developed and patented for cancer treatment purposes. These antagonists belong to two drug classes: monoclonal antibodies (mAbs) and small molecules competing with ATP and inhibiting the tyrosine kinase domain (TKIs). Three patented mAbs are currently approved in clinical cancer treatment: Trastuzumab (Herceptin) directed against HER2 and used to treat breast cancer, Cetuximab and Panitumumab which are anti-EGFR antibodies approved for colorectal cancer treatment. Unfortunately, these mAbs are facing cancer resistance mediated by paracrine activation of other ErbB members or compensatory ErbB signalling factors. In parallel, three TKIs have been approved to treat cancer: Gefitinib (Iressa®), Erlotinib (Tarceva®) inhibiting specifically EGFR and approved to treat non small cell lung cancer and Lapatinib (Tykerb®) which has the dual specificity EGFR/ HER2 and recently approved to treat metastatic breast cancer. These TKIs are also facing resistance mutations within the TK domain which increase its affinity to ATP. Resistance problems are leading to the adoption of a new strategy based on the combination of different therapies and this is likely to be the most promising future of cancer treatments. © 2008 Bentham Science Publishers Ltd.

引用

页码：181 / 187

页数：6

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