Cell plasticity in breast cancer evolution

Cancer is a disease driven by genetic and epigenetic instabilities that control and maintain aberrant signaling pathways. These aberrant behaviors are generated by accumulative mutations and epigenetic changes that allows uncontrolled growth and favor tumoral diversity of malignant phenotypes. Here, we study intrinsic cell components that contribute to its oncogenic phenotype using the collective molecular changes and stochastic genetic alterations. For extrinsic cell components, we study the features related to microenvironmental variations that influence its phenotype perturbing the course of disease. We consider that molecular changes affect microenvironment and cellular function subjecting cells to stress due to the lack of sufficient glucose and oxygen. Likewise, we identify that the estrogens play a major role in promoting the proliferation of both normal and cancer cells and the occurrence of breast cancer mutations. Finally, we incorporate these biological processes into a quantitative multiscale model to understand how microenvironmental conditions affect genetic dynamics and phenotypic diversity. Our results suggest that the evolution of malignancy and diversity in a tumor arise from and may be controlled by local cell plasticity. This supports the belief that control of local microenvironmental aspects could prevent tumor development and strongly suggest that it is possible to develop cancer treatment alternatives.