Is cancer a disease set up by cellular stress responses?

For several decades, the somatic mutation theory (SMT) has been the dominant paradigm on cancer research, leading to the textbook notion that cancer is fundamentally a genetic disease. However, recent discoveries indicate that mutations, including "oncogenic" ones, are widespread in normal somatic cells, suggesting that mutations may be necessary but not sufficient for cancer to develop. Indeed, a fundamental but as yet unanswered question is whether or not the first step in oncogenesis corresponds to a mutational event. On the other hand, for some time, it has been acknowledged the important role in cancer progression of molecular processes that participate in buffering cellular stress. However, their role is considered secondary or complementary to that of putative oncogenic mutations. Here we present and discuss evidence that cancer may have its origin in epigenetic processes associated with cellular adaptation to stressful conditions, and so it could be a direct consequence of stress-buffering mechanisms that allow cells with aberrant phenotypes (not necessarily associated with genetic mutations) to survive and propagate within the organism. We put forward the hypothesis that there would be an inverse correlation between the activation threshold of the cellular stress responses (CSRs) and the risk of cancer, so that species or individuals with low-threshold CSRs will display a higher incidence or risk of cancer.