The role of memory in non-genetic inheritance and its impact on cancer treatment resistance

Intra-tumour heterogeneity is a leading cause of treatment failure and disease progression in cancer. While genetic mutations have long been accepted as primary mechanism generating this heterogeneity, the role phenotypic plasticity becoming increasingly apparent driver intra-tumour heterogeneity. Consequently, understanding resistance key component improving cancer therapy. We develop mathematical model stochastic phenotype switching that tracks evolution drug-sensitive drug-tolerant subpopulations to clarify on population growth rates tumour persistence. By including cytotoxic therapy model, we show that, depending strategy subpopulation, can lead either transient or permanent drug resistance. study drug-resistant, genetically homogeneous non-small cell lung cells derive rational schedule drives extinction avoids competitive release sub-population. This model-informed therapeutic results increased efficacy when compared against periodic therapy, and, most importantly, sustained decay without development