Despite results of research demonstrating impressive antitumor effects in preclinical studies, new therapies often fail to show significant efficacy in clinical trials, indicating that current methods, including immortalized cancer cell lines implanted into xenograft models, are suboptimal in predicting therapeutic efficacy. Major deficiencies of immortalized cancer cell line models are a lack of heterogeneity reflective of the original malignancy and an improper microenvironment.54 The PDX model is considered to be highly relevant to actual human tumor growth because the xenograft maintains the original molecular characteristics and heterogeneity.55 Thus, PDX models could have more predictive power for translating preclinical efficacy into clinical outcomes compared to xenograft models generated from established cell lines or genetically engineered mouse models. To obtain more preclinical data, we established 3 ESCC PDX model cell lines to test the effect of DFMO on ESCC growth. Results showed that DFMO treatment significantly inhibited the progression of ESCC without reducing mouse body weight. Moreover, IHC results reconfirmed that DFMO not only suppressed proliferation, but also induced apoptosis in ESCC cells, leading to the inhibition of ESCC progression. Notably, low doses of DFMO (2%) significantly inhibited the progression of ESCC PDX tumor growth whereas the high dose (4%) did not increase the effect, suggesting that in future clinical trials, increasing the DFMO dose will not enhance its antitumor effects.