Multiple signaling pathways regulate cell proliferation and survival and are therefore important for maintaining homeostasis of development. The balance between cell growth and death is achieved through orchestrated signal transduction pathways mediated by complex functional interactions between signaling axes, among which, PI3K/Akt and Ras/MAPK as well as JAK/STAT play a dominant role in promoting cell proliferation, differentiation, and survival. In clinical cancer therapies, drug resistance is the major challenge that occurs in almost all targeted therapeutic strategies. Recent advances in research have suggested that the intrinsic pro-survival signaling crosstalk is the driving force in acquired resistance to a targeted therapy, which may be abolished by interfering with the cross-reacting network.
Keywords: Apoptosis; Cell cycle; Drug resistance; JAK/STAT; Lung cancer; Melanoma; Proliferation; Ras/MAPK; Signaling crosstalk; mTOR/PI3K/Akt.