Pancreatic cancer is a death sentence. It is quick to metastasize, hard to detect, and resistant to treatment. Following resection, radiation and chemotherapy are used to eradicate the remaining bits of the tumor that are left behind. These have not proven all that effective at leaving the patients cancer free. Pancreatic cancer is quite hard to access using chemotherapy due to its poor perfusion and desmoplastic (growth of fibrous or connective tissue) stroma. To add to confusion, the therapeutic window, the balance between toxicity and efficacy, of many chemotherapies is quite small. (The researchers refer to this as the “therapeutic index”). Additionally, chemotherapies have very short half-lives and often do not reach their desired target because of this. Researchers speculate that by increasing vasculature and preventing the accumlation of connective tissues in the stroma, chemotherapies would more easily reach and apoptose their targets.
The Hedgehog Signaling pathway is involved mainly in embryo development but also has roles in adults. In cancer, a paracrine signal between neoplastic cells and stroma cells activates the hedgehog pathway in the stroma cells and leads to stromal desmoplasia. This effectively builds a wall of connective tissues around the new cancer cells and allows for the tumor to expand without being trimmed by chemo. One of the three pathways in the hedgehog pathway, sonic the hedgehog, is over expressed in stroma cells by these new cancer cells on the perimeter of the tumor. By inhibiting the hedgehog pathway, medicine could more easily reach its target.
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