Background: It is commonly believed that cancer development is irreversible, organ-specific as well as systemic malignant disorder, often associated with harmful oxidative stress and inflammation. However, there are also well-documented cases of spontaneous cancer regression, the causative mechanisms of which are not understood. It is known that inflammation is a negative pathophysiological process that may support the development of cancer, but it is also believed that the immune system as well as oxidative stress play important roles in prevention of cancer development and defense against tumor progression. Hence, in animal models spontaneous regression of cancer could be mediated by rapid inflammatory response of granulocytes, acting against cancer mostly as innate immune response. In addition, the administration of granulocytes at the site of solid tumors can lead to tumor regression or can slow down tumor growth and extend the overall survival of animals. In both cases, similar to the radiotherapy, surgery and various chemotherapies, oxidative stress occurs generating lipid peroxidation product 4-hydroxynonenal (4-HNE). This "second messenger of free radicals" acts as growth regulating signaling molecule that exerts relatively selective cytotoxicity against cancer cells.
Conclusions: We hypothesize that abundant inflammation and metabolic changes caused by cancer and oxidative stress producing of 4-HNE may be crucial mechanisms for spontaneous cancer regression.
Keywords: 4-Hydroxynonenal (4-HNE); apoptosis; cancer; differentiation; granulocytes; growth control; inflammation; lipid peroxidation; necrosis; neutrophils; oxidative stress; polymorphonuclear cells; spontaneous regression.
© 2022 The Author(s). Published by IMR Press.