Homeostasis Back and Forth: An Eco-Evolutionary Perspective of Cancer

The role of genetic mutations in cancer is indisputable: They are a key source of tumor heterogeneity and drive its evolution to malignancy. But, the success of these new mutant cells relies on their ability to disrupt the homeostasis that characterizes healthy tissues. Mutated clones unable to break free from intrinsic and extrinsic homeostatic controls will fail to establish a tumor. Here, we will discuss, through the lens of mathematical and computational modeling, why an evolutionary view of cancer needs to be complemented by an ecological perspective to understand why cancer cells invade and subsequently transform their environment during progression. Importantly, this ecological perspective needs to account for tissue homeostasis in the organs that tumors invade, because they perturb the normal regulatory dynamics of these tissues, often coopting them for its own gain. Furthermore, given our current lack of success in treating advanced metastatic cancers through tumor-centric therapeutic strategies, we propose that treatments that aim to restore homeostasis could become a promising venue of clinical research. This ecoevolutionary view of cancer requires mechanistic mathematical models to both integrate clinical with biological data from different scales but also to detangle the dynamic feedback between the tumor and its environment. Importantly, for these models to be useful, they need to embrace a higher degree of complexity than many mathematical modelers are traditionally comfortable with.