Spelling Out CICs: A Multi-Organ Examination of the Contributions of Cancer Initiating Cells’ Role in Tumor Progression

Tumor invasion and metastasis remain the leading causes of mortality for patients with cancer despite current treatment strategies. In some cancer types, recurrence is considered inevitable due to the lack of effective anti-metastatic therapies. Recent studies across many cancer types demonstrate a close relationship between cancer-initiating cells (CICs) and metastasis, as well as general cancer progression. First, this review describes CICs’ contribution to cancer progression. Then we discuss our recent understanding of mechanisms through which CICs promote tumor invasion and metastasis by examining the role of CICs in each stage. Finally, we examine the current understanding of CICs’ contribution to therapeutic resistance and recent developments in CIC-targeting drugs. We believe this understanding is key to advancing anti-CIC clinical therapeutics. Graphical Abstract