Tissue Engineering and Breast Cancer Dormancy

There have been tremendous advances in the detection and treatment of cancer over the last 40 years leading to a significant increase in the 5 year survival rate, yet the ability to prevent, diagnose, and treat metastatic cancer remains a significant hurdle in reducing cancer associated mortality. Commonly observed prior to metastasis, is a latency period lasting a few months to several decades. This latency period is explained by cancer dormancy, a state in which cancer cells remain viable but asymptomatic and undetectable. Once conditions are favorable, dormant cells become reactivated and resume proliferation that leads to tumor growth, metastatic relapse, and ultimately poor patient outcome. While this latency period provides a window of opportunity to target and eliminate dormant cells, current chemotherapeutics fail to  target quiescent cells. Thus, to investigate the elusive factors that maintain dormancy and reactivation we have developed a 3D hydrogel platform to induce dormancy and reactivation in multiple breast cancer cell lines. The poly (ethylene glycol) (PEG)-based hydrogel consists of a cell ligating macromer, PEG-PQ, cell ligating PEG-RGDS, and a nondegradable comonomer. By tuning the concentration of PEG-RGDS and the comonomer, we developed three formulations that mimic a permissive niche (high adhesively and degradability), a non-permissive niche-1 (high adhesively and low degradability), and a non-permissive niche-2 (no adhesively and high degradability). When breast cancer cells were encapsulated in these formulations, hydrogel-induced changes led to growth and distinct forms of dormancy. We also have demonstrated the ability to reactivate dormant cells in situ. We are applying this technology to investigate mechanisms involved in dormancy-associated chemoresistance.

Read more about this exciting research!!!

Farino Reyes et al. “Tuning Hydrogel Adhesivity and Degradability to Model the Influence of Premetastatic Niche Matrix Properties on Breast Cancer Dormancy and Reactivation.” Advanced Biology. 2022.

Farino Reyes et al. “The Influence of Ligand Density and Degradability on
Hydrogel Induced Breast Cancer Dormancy and Reactivation.” Advanced Healthcare Materials. 2021.

Farino et al. “The
Influence of Matrix-Induced Dormancy on Metastatic Breast Cancer
Chemoresistance.” ACS Applied Biomaterials. 2020.

Pradhan et al.
“Tunable Hydrogels for Controlling Cancer Cell States to Model Breast Cancer
Dormancy and Reactivation.” Biomaterials. 2019.

Pradhan et al.
“Fabrication, Characterization, and Implementation of Engineered Hydrogels for
Controlling Breast Cancer Cell Phenotype and Dormancy.” MethodsX. 2019.

Pradhan et al.
“Datasets Describing Hydrogel Properties and Cellular Metrics for Modeling of
Tumor Dormancy.” DatainBrief. 2019.

Pradhan et al.
“Engineered In Vitro Models of Tumor Dormancy and Reactivation.” Journal of
Biomedical Engineering. 2018.