Page 37 - Helicobacter pylori and Gastric Cancer: From Tumor microenvironment to Immunotherapy

Abstract
Ever since its initial discovery in Drosophila, hedgehog signaling has been linked to foregut development, The mammalian genome expresses three Hedgehog paralogues, sonic hedgehog (Shh), Indian Hedgehog, and desert hedgehog. In the mucosa of the embryonic and adult foregut, Shh expression is the highest. It has now become clear that hedgehog signaling is of pivotal importance in gastric homeostasis. Aberrant activation of hedgehog signaling is associated with a range of pathological consequences including various cancers. Also in gastric cancer, clinical and preclinical data support a role of Hedgehog signaling in neoplastic transformation, and gastrointestinal cancer development, also through cancer stroma interaction. Technological advance are facilitating monitoring Hedgehog signaling broadening options for the more efficient screening of individuals predisposed to eventually developing gastric cancer and targeting Hedgehog signaling may provide opportunities for prophylactic therapy once atrophic gastritis develops. Nevertheless, convincing evidence that Hedgehog antagonists are of clinically useful in the context of gastric cancer is still conspicuously lacking. Here we analyze review the role of Hedgehog in gastric physiology and the potential usefulness of targeting Hedgehog signaling in gastric cancer.
Mini-abstract
Hedgehog signaling has a pivotal role in gastric development and homeostasis but also appears to associated with neoplastic transformation, and further development towards invasive carcinoma in the stomach. Thus monitoring Hedgehog signaling may provide an opportunity for more efficient screening of subjects predisposed to developing gastric cancer. Targeting Hedgehog signaling may be useful for prophylactic therapy once atrophic gastritis develops. Although Hedgehog antagonists have been used for other cancer types, data documenting its clinical usefulness in gastric are conspicuously lacking, and studies aimed at providing definitive answers here are called for.
MeSH keywords
Patched, Receptors; Smoothened Receptor; Zinc Finger Protein GLI1, Precision Medicine
Gastric cancer and the Hedgehog Signalling
Gastric cancer and Hedgehog signalling
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