Cancer differentiation therapy dynamics in a hybrid model of avascular tumor growth

Abstract

Cancer is not one disease but many, making it very difficult to successfully develop

treatments that effectively end it. Yet, a very promising approach still underde- veloped is differentiation therapy (DTH). As it has long been demonstrated, most

tumors are conformed by a cell population a great part of which is poorly differ- entiated, exhibiting a loss of communication and tissue homeostasis among other

things. As a result, they can achieve several hallmarks essential to their identity and chances of success. DTH has been proposed to be an efficient therapy and can be combined with cytotoxic-based therapies, and successfully used as a treatment

for acute promyelocytic leukemia (APL). However, DTH has failed so far when deal- ing with solid tumors. Why? It has been suggested that the high degree of spatial

intra-tumoral heterogeneity combined with the resilience of CSCs and their capa- bility to repopulate tumors by themselves might act as a firewall to DTH drugs. In

order to test this possibility and assess the effects of DTH on solid tumors, we pro- pose a mathematical and computational study of DTH using a spatially extended

avascular tumor model. The results obtained support the previous hypothesis and indirect evidence concerning the role of space and cancer tissue architecture.