Introduction to cell stress responses in cancer: The big picture

Cancer represents a major medical challenge of our time, exacerbated by the paradoxical combination of an age-related increase in cancer incidence and a demographic shift towards older populations worldwide. During the last 10 years, significantly improved strategies for molecular cancer prevention and targeted therapeutic intervention have become available, an encouraging sign indicating that decades of global commitment to biomedical research, implementing what is now known as the biological revolution of the late twentieth century, start bearing fruit for cancer patients and survivors. It has now become apparent that oncogene-driven tumorigenesis is associated with specific stress phenotypes including DNA damage stress, mitotic stress, metabolic stress, proteotoxic stress, and oxidative stress. Importantly, cancer cells depend on the counter-regulatory activation of cytoprotective stress response pathways enabling adaptive capabilities that antagonize the cytotoxic consequences of oncogenesis-associated cellular stresses, and cumulative research indicates that the essential nature of these stress response pathways represents a specific molecular vulnerability amenable to therapeutic intervention targeting this emerging Achilles heel of malignancy.