Cancer recurrence is one of the most imminent problems in the current world of medicine, and it is responsible for most of the cancer-related death rates worldwide. Long-term administration of anticancer cytotoxic drugs may act as a double-edged sword, as necrosis may lead to renewed cancer progression and treatment resistance. The lack of nutrients, coupled with the induced hypoxia, triggers cell death and secretion of signals that affect the tumor niche. Many efforts have been made to better understand the contribution of hypoxia and metabolic stress to cancer progression and resistance, but mostly with respect to inflammation. Here we provide an overview of the direct anticancer effects of necrotic signals, which are not necessarily mediated by inflammation and the role of DAMPs (damage-associated molecular patterns) on the formation of a pro-cancerous environment.
Keywords: Angiogenesis; Anti-angiogenic therapy; Cancer; Chemotherapy; DAMPs; Hypoxia; Metabolic stress; Metronomic therapy; Necrosis; Recurrence; Resistance; Tumor microenvironment.