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Ref Type Journal Article
PMID (24300914)
Authors Ding X, Qu X, Fan Y, Che X, Qu J, Xu L, Liu J, Liu Y
Title Trastuzumab and oxaliplatin exhibit a synergistic antitumor effect in HER2-postive gastric cancer cells.
Journal Vol Issue Date Pages Journal Short Title
Anti-cancer drugs 25 3 2014 Mar 315-22 Anticancer Drugs
URL
Abstract Text Trastuzumab has recently been recommended for the treatment of epidermal growth factor receptor-2 (HER2)-positive advanced gastric cancer in combination with the capecitabine/cisplatin (XP) versus continuous infusion of 5-fluorouracil/cisplatin (FP) regimen. However, it is unclear whether it is rational to combine trastuzumab with other chemotherapy regimens in clinical practice. Our study demonstrates that adding trastuzumab to oxaliplatin, a commonly used third-generation platinum derivative, increases the antitumor effect in vitro. In MTT assays, combination treatment with oxaliplatin and trastuzumab significantly decreased the concentration of oxaliplatin required to induce 50% growth inhibition in HER2-positive gastric cancer cells. Further investigation revealed that the trastuzumab-oxaliplatin combination induced cell cycle arrest and decreased expression of both p-AKT and p-ERK. Notably, this treatment combination induced downregulation of the excision repair cross-complementation group 1 (ERCC1) protein, which is involved in the key repair process of the oxaliplatin-DNA platinum adduct at the protein level. Similar changes were also observed in HER2-positive breast cancer cells. These findings suggest that trastuzumab synergizes the cytotoxic effect of oxaliplatin on HER2-positive gastric and breast cancer cells. Our study provides preclinical evidence for the optimization of this combination regimen in the treatment of HER2-positive gastric cancer patients.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References