Breast Cancer - EMT6 Tumor Model

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Breast cancer is the most commonly diagnosed cancer among women in the United States and the fourth leading cause of cancer death. Early detection initiatives together with improved treatment options have resulted in an increase in the 5-year overall survival rate from 75% in 1975 to over 90% today. Despite these favorable survival statistics, metastatic disease continues to be a treatment challenge and often results in death. For this reason, the continual development of new treatments for breast cancer is necessary.

While several treatment options are available to fight hormone- or Her2-driven breast cancer, options are somewhat limited for triple negative breast cancer patients who cannot take advantage of these targeted therapies. Adding to this problem, despite success with immunotherapies in treating melanoma and lung cancer, breast cancer has proven to be especially difficult to treat by checkpoint blockade or other immunotherapies. However, with the focused effort in research toward immuno-oncology approaches to breast cancer, emerging clinical data is showing promise, particularly in combination therapy. The EMT6 tumor model is used to help drive this research forward. Derived from a transplanted hyperplastic aveolar nodule in BALB/c mice, this model takes advantage of the complete mouse immune system and serves as a powerful tool in the immune-oncology space.

We have established the syngeneic Mouse Breast Cancer Model using EMT6 cells to evaluate response of immune-oncology agents in a triple negative breast cancer model. In vitro, these cells grow as an adherent population with an epithelial morphology. In vivo, subcutaneous implantation of the EMT6 cells in BALB/c female mice, results in consistent and rapid growth at a variety of inocula with a doubling time of approximately 3-4 days. Control animals stay on study for 25-30 days before reaching euthanasia criteria of excessive tumor burden. This results in a model which can facilitate up to a three-week dosing window for test agents to elicit their anti-tumor activity

Growth kinetics validation.  5 x 10EMT6 mouse breast cancer model cells (derived from BALB/cCrgl female mice) were subcutaneously injected into the rear flank of BALB/c mice. Tumor growth volume was monitored approximately twice / week using calipers (Data are mean± SEM; n=15).

EMT6 tumor model validation with Cyclophosphamide.  5 x 10EMT6 mouse breast cancer model cells were subcutaneously injected into the rear flank of BALB/c mice. Once mean tumor size reached 75-100 mm3, mice were randomized int groups and treated with chemotherapy.  Tumor growth volume was monitored approximately twice / week using calipers (Data are mean± SEM; n=15).

EMT6 cells are know to be resistant to cisplatin and have also been previously reported to be susceptible to cyclophosphamide.

The EMT6 tumor model can be run either subcutaneously or orthotopically.  In addition to tumor volume a variety of additional physiological parameters and biomarkers, such as cytokine levels,  can be incorporated into the study design.  Furthermore, a luciferase-tagged EMT6 line is available allowing for the study of metastatic processes using IVIS imaging.