Mouse models for cancer dormancy and recurrence
Breast cancer recurrence and metastasis from activated dormant tumors remain the leading causes in disease morbidity. Here, we provide a brief review of studies that utilize mouse models to dissect the mechanisms of dormancy and therapeutic strategies to avert recurrence. This review specifically accentuates the versatility and benefits of immunocompetent transgenic mouse models that can be manipulated to recapitulate primary dormancy, metastatic dormancy, and post-therapy dormancy.
PI3K H1047R mutation and its anti-metastatic potential
We explored the role of a PI3K mutation commonly found in breast cancer patients using transgenic model and discovered a unique activity of PI3K H1047R mutation in the context of Her2-induced cancer. In contrast to its well-defined oncogenic potential, PI3K H1947R mutation promotes non-invasive carcinoma with reduced metastatic potential. This model is therefore a valuable preclinical model allowing us to investigate therapeutic options targeting this mutation in breast cancer.
Cancer cell intrinsic and extrinsic mechanisms of recurrence
Mammary epithelial-specific deletion of β1 integrin captures breast cancer dormancy and recurrence in vivo. We demonstrate that dormancy in our model is regulated by p53-dependent cellular senescence and that pro-tumourigenic stromal cues and intrinsic genetic mutation are required for dormancy exit.