Disease mortality. But w If the success of trastuzumab is a consequence of the HER2 oncogene hypothesis, it is not enough to validate. Validation of the oncogene hypothesis implies that patients with signs mechanistic inactivation of tumor HER2 trastuzumab. This evidence is currently lacking and more work for decades, in an attempt to further evaluate the mechanism of producing trastuzumab to identify Ispinesib SB-715992 prospects Tenteils gr convince contradictory and inconclusive, and a mechanistic model, and if it inhibits fa trastuzumab, the function of the HER2 oncogene was initiated. Extensive studies over the last decade have attempted to understand the molecular mechanisms of tumor development clinical activity determine t to trastuzumab against T.
The easiest assumption is based on the predetermined mAb and anti-HER2 mAb 4D5 Neut data showing that these monoclonal Body CYC202 degradation Zieloberfl che derived HER2 or induce Neut prepared. Although this seems a simple test fa cl Ture end One contradictory analysis by entering many researchers studying the effects of trastuzumab for HER2 expression in tumor cells results also with the likes of Ren cellular His reindeer assays. W Although some studies have shown that HER2 trastuzumab downregulated in tumor cells overexpressing HER2, other studies clearly show that this is not the case. Part of the complexity decided t Of T in this area was St when it was found that trastuzumab binds and internalizes a bottle surface Surface HER2, but r??appara t with HER2 on the surface Surface of Che, but only passively accompany HER2 along the normal endocytic recycling.
The most convincing proof at this point seems to be the position that trastuzumab is not the cause of down-regulation of HER2 in tumor cells may be better term. As a result, three clinical studies have not demonstrated a reduced expression of HER2 tumors in patients treated with trastuzumab. Therefore, it seems unlikely that the antitumor activity of t Is mediated by downregulation of T of trastuzumab in HER2 tumors. Page 5 Moasser Oncogene. Author manuscript 6th, April 2011 PMC. The h Important most frequent hypothesis that streamline development of trastuzumab and other anti-HER2 monoclonal rpern For most of the nineties, it inhibits the activation of HER2 by unknown ligands.
However, the adoption HER2 ligand has never been discovered, and screens, biochemical studies of the contribution of the genome of the calculation and the revelations of the crystal structure clearly shows that HER2 has no physiological ligand and ligand-sensitive functions activated by heterodimerization with its ligand to its partners, taught family. Tats Chlich the return has HER2 extracellular Ren Cathedral a constitutively active conformation, the state of the ligand bound to other proteins Family, the M Exclude possibility of activating M r T as ligands S. Thus, the assumption that the ligand binding of trastuzumab and direct activation of HER2 inhibits all but rejected at that time. Another hypothesis that has been put forward that trastuzumab interaction of HER2 with m or family SES inhibits possible to change that other interacting proteins. convincing evidence for this hypothesis has not made an appearance. In tests after trastuzumab does not inhibit HER2 HER3 interaction, fluorescence and r