Treatment Of HER2-overexpressing Cancer Research Articles

Systemic investigation of inetetamab in combination with small molecules to treat HER2-overexpressing breast and gastric cancers.

Most patients with metastatic breast cancer or gastric cancer who are treated with trastuzumab, an anti-HER2 monoclonal antibody, become refractory to the drug within a year after the initiation of treatment. Although the combination of trastuzumab with pertuzumab produced synergetic effects in the treatment of HER2-overexpressing cancers, not all patients with HER2 overexpression benefited from the trastuzumab plus pertuzumab combination. To improve the clinical benefits of trastuzumab, we systemically investigated the combination of inetetamab (Cipterbin), an analog of trastuzumab, with a variety of small molecules, including tyrosine kinase inhibitors (TKIs) and chemotherapeutic agents in vivo. We showed that pan-TKIs-induced synergistic antitumor effects with inetetamab in the treatment of these two types of cancers and that adding chemotherapeutic agents to the existing TKI plus anti-HER2 monoclonal antibody combination strategies induced additional inhibitory effects, suggesting that such combination strategies may be choices for the treatment of these two tumors. Thus, combination therapies targeting distinct and broad pathways that are essential for tumor growth and survival can be effective for treating metastatic breast cancers and gastric cancers.

Targeted treatment strategies for patients with trastuzumab-resistant HER2-overexpressing breast cancer

Trastuzumab combined with chemotherapy improves overall response rate in women with HER2-overexpressing breast cancer.However,therapeutic resistance to trastuzumab typically occurs after several months of starting therapy and overall survival does not improve significantly.Studies have reported that the potential mechanisms of resistance to trastuzumab are mainly related to the signal pathway activation from receptor tyrosine protein kinases outside of the HER family and the amplification of the PI3K-AKT pathway.Novel target therapies such as tyrosine kinase inhibitors,PI3K inhibitors are approved as substitutes for the treatment of HER2-overexpressing breast cancer,but the response to each single-agent tends to be short-lived.Several large randomized adjuvant trials have showed that novel molecular targeted therapies combinations will markedly limit or eventually abrogate acquired resistance to primary trastuzumab therapy. Key words: Receptor, epidermal growth factor; Breast neoplasms; Drug resistance

Suppression of tumor growth in human gastric cancer with HER2 overexpression by an anti-HER2 antibody in a murine model.

New modalities are necessary for the treatment of patients with unresectable gastric cancer. The aim of this study was to investigate whether or not anti-HER2 antibody could suppress the growth of human gastric cancer cells with HER2 overexpression in vitro and in vivo. Four human gastric cancer cell lines, NCI-N87, MKN-45P, Kato-III, and MKN-1, were used in this study. The suppression of cell proliferation in vitro and of subcutaneous tumor growth in a nude mouse model after treatment with trastuzumab was examined. The expression of HER2 protein was investigated by Western blot analysis. The effect of trastuzumab on the survival rate of nude mice with peritoneal dissemination was examined. Trastuzumab significantly reduced proliferative activity in NCI-N87, a HER2-overexpressing human gastric cancer cell line, in vitro. In the nude mouse model with transplanted subcutaneous tumor, trastuzumab significantly suppressed the tumor growth of NCI-N87 cells, and then HER2 expression was reduced. Trastuzumab improved the survival rate of mice with peritoneal dissemination of MKN-45P cells. Trastuzumab therapy is a potential candidate for a novel treatment of HER2-overexpressing gastric cancer.