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.