Understand the role of chemotherapeutic gradient in the emergence of polyploid giant cancer cells using mean field model*

Polyploid giant cancer cells (PGCCs) have been shown to correlate with poor response to chemotherapy and contribute to tumor heterogeneity regulation through asymmetric cell division [1][2]. However, most in vitro cancer studies do not replicate the complexity of in vivo tumors, while animal models are difficult to study in a comprehensive manner. The dynamics of PGCC emergence remain unclear in the context of the complex heterogeneity of the tumor ecosystem. In a recent paper, we presented the Evolution Accelerator (EA) [3], which allowed the quantitative study of the interactions of multiple cell types on a chemotherapy gradient. Utilizing the EA technology, we discovered that a docetaxel gradient greatly elevated the emergence of PGCCs and increased survival of the cancer population. With population analysis and careful experimental control, we demonstrated with a simple mean field model that the coexistence of the emerging drug-resistance PGCCs and proliferative diploid cells may serve as a survival strategy for the cancer population.

1 Karuna Mittal et al., British Journal of Cancer, 116(9):1186-1194, 2017.
2 Shiwu Zhang et al., PLoS ONE, 8(11):1-16, 2013.
3 Ke-Chih Lin et al., Convergent Science Physical Oncology, 3(4):045001, 2017.