Evaluation of the treatment strategies on patient-derived xenograft mice of human breast tumor.

Abstract Since only a minority of patients may respond to single-agent therapies, methods to test the potential antitumor activity of rational combination therapies are still needed. This study aimed to characterize the efficacy of antitumor combination therapies in vivo within the primary tumor using patient-derived xenograft (PDX) models by gamma-irradiation-induced immune suppression. We employed four Luminal A PDX models obtained from human mammary tumors grown in mice. PDX models were implanted into the right flank of mice, and treatments have ensued once tumor volume reached ∼150 mm3. Four of the active drugs— Adriamycin, Cyclophosphamide, Taxotere, and Tamoxifen—were tested in vivo to treat mammary tumors. The tumor volume was measured during the study. The mice's immune system was inherently suppressed by gamma irradiation, thus allowing human tumors to grow. The results showed that the tumorigenesis rate of the PDX model was from 65 to 80%. PDX models were successfully established with a high frequency of tumor engraftment. Humanized mice treated with a two-drug regimen, that is, adriamycin + cyclophosphamide exhibited an increased antitumor response than a three-drug regimen, that is, adriamycin + cyclophosphamide + taxotere that correlated with tumor growth inhibition. Combination therapies with adriamycin + cyclophosphamide in PDX mice reduced tumor growth in four Luminal A PDX models. These preclinical results suggest that a two-drug regimen than a three-drug regimen can be useful for breast cancer patients. This study provides insights for future studies combining chemotherapeutics with targeted therapies using PDX models by gamma-irradiation-induced immune suppression.