Cancer is a burdensome and challenging disease. Existing treatments, including chemotherapy and radiotherapy, are effective in reducing primary tumor burden. However, metastatic growths in distant organs can emerge years later, which may be lethal. Breast cancer, especially, is prone to seeding dormant metastases throughout the body. Furthermore, there is a growing body of evidence suggesting that these treatments may actually promote metastatic resurgence. Successful, long-term treatment of breast cancer depends on understanding the process by which dormant, disseminated tumor cells reawaken and become proliferative once more. A major barrier to developing such understanding is the lack of breast cancer models capable of recapitulating this phenomenon. Often, host organisms perish from primary tumor burden before dormant breast cancer cells can reawaken. To address this need, novel breast cancer models were developed to recapitulate the dormant cancer niche.

An implantable, microporous, polyacrylamide scaffold developed by the Lee lab were implanted subcutaneously into PyMT-MMTV mice which spontaneously generate breast tumors. Implanted scaffolds captured circulating breast tumor cells. Implanted scaffolds were serially transplanted into tumor-free mice to avoid primary tumor induced morbidity. Immunohistochemistry (IHC) was used to confirmed capture of DTC’s. Captured tumor cells remained dormant for up to 24 weeks in vivo following transplantation.

To investigate implications of inflammation, scaffolds were intentionally disrupted via biopsy punch following serial transplantation. Disrupted scaffolds were capable of developing overt metastasis, and showed a higher population of cancer cells, linking ECM remodeling to metastatic relapse, and suggesting that disruptive treatment modalities may carry metastatic risk.

Lastly, biomaterial platforms were created to more accurately model the bone environment to support future breast to bone metastasis modeling. Demineralized trabecular bone scaffolds were seeded with bone marrow cells and implanted subcutaneously in mice. The trabecular pore space was filled with polyacrylamide in order to attract circulating tumor cells to this bone environment and crushed bone powder in order to promote mineralization in-vivo.

These results suggest that an implantable based model will be an enabling tool to study the progression of dormant niches and the effect of treatment on the development of these niches. Isolating the dormant niche in this manner will yield unique opportunities to develop treatments that specifically target dormant cancer.