Tumor relapse and metastasis remain major obstacles for improving overall cancer survival. Tumor initiating cells (TICs) also referred to as cancer stem-cells (CSCs) may be responsible for invasion, metastasis and tumor heterogeneity. TICs exhibit tumorigenic properties and the ability to self-renew, form differentiated progeny, and develop resistance to therapy. TICs use signaling pathways that are found in normal stem cells, such as Wnt, Notch, and Hedgehog (Hh), as well as other signaling pathways and modifications to the microenvironment. The origin of TICs is not understood, but data suggest that they develop from a primordial cell, or possibly other cancer cells that develop aberrant genetic events early in cancer development. Therapeutic targeting of TICs and bulk tumor populations may provide a strategy to suppress tumor re-growth. Development of agents that target critical steps in the Wnt, Notch, and Hh pathways will be complicated by signaling cross-talk. The role that embryonic signaling pathways play in the function of TICs, the development of new anti-TIC therapeutic agents, and the complexity of signaling cross-talk will be described and the controversies related to �stem cells� discussed.

Identification of the tumor initiating cell and treatment strategies for its eradication by inhibiting embryonic pathway signaling

246th National Meeting (2013)

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