The paradox of cooperation among selfish cancer cells.

It is traditionally assumed that during cancer development, tumor cells abort their initially cooperative behavior (i.e., cheat) in favor of evolutionary strategies designed solely to enhance their own fitness (i.e., a "selfish" life style) at the expense of that of the multicellular organism. However, the growth and progress of solid tumors can also involve cooperation among these presumed selfish cells (which, by definition, should be noncooperative) and with stromal cells. The ultimate and proximate reasons behind this paradox are not fully understood. Here, in the light of current theories on the evolution of cooperation, we discuss the possible evolutionary mechanisms that could explain the apparent cooperative behaviors among selfish malignant cells. In addition to the most classical explanations for cooperation in cancer and in general (by-product mutualism, kin selection, direct reciprocity, indirect reciprocity, network reciprocity, group selection), we propose the idea that "greenbeard" effects are relevant to explaining some cooperative behaviors in cancer. Also, we discuss the possibility that malignant cooperative cells express or co-opt cooperative traits normally expressed by healthy cells. We provide examples where considerations of these processes could help understand tumorigenesis and metastasis and argue that this framework provides novel insights into cancer biology and potential strategies for cancer prevention and treatment.

On the need for integrating cancer into the One Health perspective.

Recent pandemics have highlighted the urgency to connect disciplines studying animal, human, and environment health, that is, the "One Health" concept. The One Health approach takes a holistic view of health, but it has largely focused on zoonotic diseases while not addressing oncogenic processes. We argue that cancers should be an additional key focus in the One Health approach based on three factors that add to the well-documented impact of humans on the natural environment and its implications on cancer emergence. First, human activities are oncogenic to other animals, exacerbating the dynamics of oncogenesis, causing immunosuppressive disorders in wildlife with effects on host-pathogen interactions, and eventually facilitating pathogen spillovers. Second, the emergence of transmissible cancers in animal species (including humans) has the potential to accelerate biodiversity loss across ecosystems and to become pandemic. It is crucial to understand why, how, and when transmissible cancers emerge and spread. Third, translating knowledge of tumor suppressor mechanisms found across the Animal Kingdom to human health offers novel insights into cancer prevention and treatment strategies.