The combinational therapy of trastuzumab and cetuximab inhibits tumor growth in a patient-derived tumor xenograft model of gastric cancer

ABSTRACT

Purpose: Gastric cancer (GC) is one of the leading causes of cancer mortality worldwide. Although therapeutic strategies for GC have improved, the prognosis for advanced GC remains poor. Herein, the present study sought to design a personalized cancer therapy specific to a stage III GC patient. Methods: The tumor was surgically removed and was used to establish a patient-derived tumor xenograft (PDTX) model utilizing nude mice. Various molecular-targeted anticancer treatments were tested in the study, including control (no treatment), bevacizumab, cetuximab, bevacizumab + cetuximab, trastuzumab, and trastuzumab + cetuximab. Results: Trastuzumab + cetuximab treatment exhibited the best antitumor growth effect, followed by trastuzumab, bevacizumab + cetuximab, cetuximab, and bevacizumab. Similarly, trastuzumab + cetuximab was also the most effective treatment at inducing apoptosis and cell cycle arrest in primary cultures of the patient’s gastric cancer cells. Among all treatments tested in the study, trastuzumab + cetuximab showed the most profound effect in reducing the protein expression of proliferation and metastatic markers (VEGF, MMP-7, EGFT, Ki-67 and, PCNA) in tumors obtained from PDTX models, which may be the mechanism underlying the profound antitumor growth effect exerted by trastuzumab + cetuximab. Conclusions: The data indicate that trastuzumab + cetuximab combinational therapy should be the most effective antitumor growth therapy for the GC patient whom we took the cancer cells from (AU)

RESUMEN

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