Several evidences demonstrate that embryogenesis and tumorigenesis have common characteristics, where both processes depend on coordinated mechanisms of proliferation, differentiation and migration. The best-studied function of Shh, during mouse embryogenesis, is to instruct neural progenitors patterning, in which it is possible to distinguish six different cell types based on molecular markers, such as interneurons progenitors and motor neurons, that differentiate due to a gradient of Shh. Dhh is restricted to the gonads including granulosa cells of ovaries and sertoli cells of testis. Shh has particularly marked roles in nervous system cell type specification and limbs patterning, whereas Ihh has important roles in skeletal development, mainly endochondral ossification. Shh and Ihh have important, and sometimes coinciding, functions in several tissues.
There are three mammalian Hh proteins, Shh, Indian-Hedgehog (Ihh), and Desert-Hedgehog (Dhh). This organelle is important to process several cellular signals and/or extracellular environmental changes necessary for animal development, as Wingless (Wnt), Platelet-derived growth factor (PDGF), Shh, and Notch. The PC is an organelle, microtubule-based, that emerges from the cell surface of most vertebrate cells. The vertebrate Hh signaling is not entirely dependent on an extremely specialized organelle, the primary cilium (PC), unlike other essential developmental signaling pathways. Further, Hh signaling is disrupted in diverse types of cancer. Hh is important for the organogenesis of almost all organs in mammals, as well as in regeneration and homeostasis. Hedgehog (Hh) is one of few of signaling pathways that is frequently used during development for intercellular communication. In this review, we will also highlight some clinical trials that use the Shh pathway as a target for treating brain cancer. So, a better knowledge of Shh signaling pathway opens an avenue of possibilities for the treatment of not only for brain tumors but also for other types of cancers. Shh can signal through a canonical and non-canonical way, and it also has important points of interaction with other pathways during brain tumorigenesis. Therefore, emerging studies are being conducted in order to find new inhibitors for Shh signaling pathway, which could be safely used in clinical trials. So, a better knowledge of the Shh pathway opens an opportunity for targeted therapies against brain tumors considering a multi-factorial molecular overview. Most of the brain tumors are resistant to chemotherapeutic drugs, consequently, they have a poor prognosis. It is already known that Sonic hedgehog (Shh) pathway is important for the evolution of radio and chemo-resistance of several types of tumors. Hedgehog (Hh) signaling pathway plays an essential role during vertebrate embryonic development and tumorigenesis.
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