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|Ref Type||Journal Article|
|Authors||Barok M, Tanner M, Köninki K, Isola J|
|Title||Trastuzumab-DM1 is highly effective in preclinical models of HER2-positive gastric cancer.|
|Date||2011 Jul 28|
|Abstract Text||A novel antibody-drug conjugate (trastuzumab-DM1, T-DM1) is currently in clinical trials for patients with trastuzumab resistant HER2-positive breast cancer. Since no clinical data is available from gastric cancer, we studied T-DM1 on HER2-positive human gastric cancer cells and xenograft tumors.Effects of T-DM1 were studied in four HER2-positive gastric cancer cell lines (N-87, OE-19, SNU-216 and MKN-7) in vitro. Xenograft tumors from N-87 and OE-19 were studied to determine the effect of T-DM1 in vivo.T-DM1 was found more effective than trastuzumab in N-87 and OE-19, and moderately effective in MKN-7 cells. On SNU-216 cells both trastuzumab and T-DM1 showed limited efficacy. In xenograft tumor experiments, complete pathological response was observed in all OE-19 xenografted mice and in half of the N-87 xenografted mice. The results were equally good irrespective of the tumor burden at therapy initiation, or preceding trastuzumab treatment. T-DM1 treatment showed direct effects (apoptotic cell death and aberrant mitosis) as well as it mediated antibody-dependent cellular cytotoxicity (ADCC).T-DM1 showed a promising anti-tumor effect in HER2-positive gastric cancer cell lines in vitro and in vivo, even in tumors which had developed resistance to trastuzumab. T-DM1 therapy may warrant clinical trials for HER2-positive gastric cancer patients.|
|Molecular Profile||Treatment Approach|
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|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
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|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
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|ERBB2 over exp||stomach cancer||sensitive||Ado-trastuzumab emtansine||Preclinical - Cell line xenograft||Actionable||In a preclinical study, Kadcyla (trastuzumab emtansine) inhibited tumor growth in human cell line xenograft models of gastric cancer with ERBB2 (HER2) amplification and over expression (PMID: 21458915).||21458915|
|ERBB2 amp ERBB2 over exp||stomach cancer||sensitive||Ado-trastuzumab emtansine||Preclinical - Cell line xenograft||Actionable||In a preclinical study, Kadcyla (trastuzumab emtansine) inhibited tumor growth in human cell line xenograft models of gastric cancer with ERBB2 (HER2) amplification and over expression (PMID: 21458915).||21458915|