Heterogeneity-related anticancer therapy response differences in metastatic colon carcinoma: new hints to tumor-site-based personalized cancer therapy.

BACKGROUND: Heterogeneity in primary tumor and related metastases may result in different response to anticancer therapy. Previous work revealed that there were heterogeneity in primary colon carcinoma and matched lymphatic and hepatic metastases. Subsequent study further ascertained the different expression of some functional genes in primary colon carcinoma and paired hepatic metastases in a larger group of patients with metastatic colon carcinoma. However, whether such heterogeneity in primary colon carcinoma and corresponding lymphatic and hepatic metastases would result in different response to anticancer therapy is unknown.METHODOLOGY: To investigate whether the heterogeneity in primary colon carcinoma and matched lymphatic and hepatic metastases would result in different response to anticancer therapy, patient-derived tumor tissue (PDTT) xenograft models of colon carcinoma with lymphatic and hepatic metastases were used to evaluate the response to VEGF-targeted therapy (bevacizumab) in combination with chemotherapy (capecitabine).RESULTS: All xenografts of primary colon carcinoma and corresponding lymphatic and hepatic metastases in nude mice responded to VEGF-targeted therapy (bevacizumab) in combination with chemotherapy (capecitabine). However, chemotherapy (capecitabine) alone resulted in significantly higher tumor growth inhibition rate in xenogfafts of primary colon carcinoma than that of corresponding lymphatic and hepatic metastasis (P < 0.01). VEGF-targeted therapy (bevacizumab) in combination with chemotherapy (capecitabine) resulted in significantly higher tumor growth inhibition rate in xenogfafts of colon carcinoma lymphatic metastasis than that of corresponding primary colon carcinoma and hepatic metastasis (P < 0.001).CONCLUSION: Our results demonstrate that primary colon carcinoma and its corresponding lymphatic and hepatic metastases have different response rate to chemotherapy (capecitabine) and to VEGF-targeted therapy (bevacizumab) in combination with chemotherapy (capecitabine). This study provides us new hints to tumor-site-based personalized cancer therapy in metastatic colon carcinoma.