BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
BACKGROUND: 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 humangastric cancer cells and xenograft tumors. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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 cancerpatients.
Authors: Katsuya Nagaoka; Xuewei Bai; Kosuke Ogawa; Xiaoqun Dong; Songhua Zhang; Yanmei Zhou; Rolf I Carlson; Zhi-Gang Jiang; Steve Fuller; Michael S Lebowitz; Hossein Ghanbari; Jack R Wands Journal: Cancer Lett Date: 2019-02-12 Impact factor: 8.679
Authors: Adriana V F Massicano; Supum Lee; Bryant K Crenshaw; Tolulope A Aweda; Retta El Sayed; Ian Super; Ron Bose; Bernadette V Marquez-Nostra; Suzanne E Lapi Journal: Cancer Biother Radiopharm Date: 2019-01-24 Impact factor: 3.099
Authors: Humaid O Al-Shamsi; Yazan Fahmawi; Ibrahim Dahbour; Aziz Tabash; Jane E Rogers; Jeannette Elizabeth Mares; Mariela A Blum; Jeannelyn Estrella; Aurelio Matamoros; Tara Sagebiel; Catherine E Devine; Brian D Badgwell; Quan D Lin; Prajnan Das; Jaffer A Ajani Journal: J Gastrointest Oncol Date: 2016-08