Cancer develops from mutations in stem and progenitor cells. Patients suffering from esophageal squamous cell carcinoma are commonly treated by a combination of chemotherapy and esophagectomy, a debilitating surgical procedure. My group have identified heterogeneity within the esophageal progenitor population in homeostasis which is likely to have implications for the development of squamous cell carcinomas of the esophagus, lead to targeted therapeutic strategies and hopefully reduce the need for surgical intervention. Stem and progenitor cells reside in a complex microenvironment, or niche, that is instructive in determining cell fate during homeostasis and tumor initiation. In the morphologically uniform esophageal epithelium, the presence of progenitor subpopulations cells as well as local microenvironmental niches is not evident. My group aim to not only delineate the functional heterogeneity within the esophageal progenitor population during homeostasis and cancer development, but also map out and eventually target the stromal niche cells driving this phenotypic epithelial heterogeneity. Furthermore, we will use a clinically relevant platform to screen for druggable targets with the ability to eliminate esophageal tumor initiating cells. The incidence of human esophageal squamous cell carcinomas is dramatically increasing, and delineation of the esophageal stem cell niche is a vital first step towards identifying new combined therapeutic strategies directed at eliminating this cancer.
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