The Special Role of JAK/STAT, and Notch Signaling Pathways in Cancer Pathogenesis

Abstract

Cancer is essentially a genetic disease, characterized by unclear etiology in many cases, complex pathogenic mechanisms, since in the majority of cancer cases only risk or predisposing factors have been recognized, and unclarified observations concerning organs that are not often affected by malignant tumors such as the small intestine, spleen, heart, and the neurons of the Central Nervous System. A tumor’s appearance and progression presupposes a series of genetic and non-genetic alterations that characterize tumor cells, and are related to self-sufficiency in growth stimuli, insensitivity to anti-growth signals, unlimited replicative potential, angiogenesis promotion, ability to infiltrate surrounding tissues and induce distant metastases, and resistance to apoptosis. The mentioned characteristics are associated with signaling pathways that are involved in cell survival, cell death, cell growth and division, cell motility, and can be considered in the context of abnormalities of wider signaling networks that support cancer progression, such as tumor microenvironment alterations, angiogenesis, and inflammation. Among others, two signaling pathways, JAK/STAT and Notch, seem to play essential roles in tumorigenesis, despite the fact that are implicated in diverse cellular functions such as tissue formation and cell differentiation, proliferation, apoptosis, inflammation, self-renewal, antitumor immune response suppression, motility, stress response and other responses depending on the target tissue. Hyperactivation of those signaling pathways caused by mutations are able to transform cellular proto-oncogenes to oncogenes, whereas inactivation of tumor suppressor genes eradicates crucial negative regulators of signaling. Various anticancer agents target those signaling pathways in an attempt to inhibit those pathways including monoclonal antibodies and other agents in the context of targeted cancer therapy.