Cancer stem cells are a sub-population of cancer cells that can proliferate extensively, give rise to differentiated cells and form new tumors. None of the existing anticancer therapies effectively target this cell population which is thought to be the root cause of drug resistance and cancer recurrence.
A research team led by Prof. Ying-Jie Wang at the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital of School of Medicine, Zhejiang University has now identified an endogenous small molecule that specifically targets cancer stem cells and exhibits potent anticancer activity. The team found that ITE, a tryptophan derivative that acts as an endogenous AhR ligand, can enhance the binding of the AhR to the promoter of Oct4 and suppress its elevated transcription induced by tryptophan deprivation or hypoxia. Consequently, synthetic ITE induced the differentiation of cancer stem cells and reduced their tumorigenic potential in both subcutaneous and orthotopic xenograft tumor models.
This work was published in Nature Communications on June 10, 2015. It reveals a novel direct connection between Oct4 and the AhR pathway, and opens a new therapeutic avenue to targeting cancer stem cells.