BDNF and cancer: Increasing evidence has point out that neural signals are required for the development and regeneration of tissues by interacting with stem/progenitor cells in tissues including skin, kidney, and bone marrow.61–63 Activation of adrenergic signaling leads to “unhealing wounds” resembling the tumor microenvironment.64 Thus, cancer cells could construct the innervation patterns through secreted factors (e.g. NGF and BDNF) to drive a self-assembled neural-cancer circuits that favors cancer stemness.