The cancer stem cell paradigm: a new understanding of tumor development and treatment

Abstract

Importance of the field: Cancer is the second leading cause of death in the United States, and therefore remains a central focus of modern medical research. Accumulating evidence supports a 'cancer stem cell' (CSC) model - where cancer growth and/or recurrence is driven by a small subset of tumor cells that exhibit properties similar to stem cells. This model may provide a conceptual framework for developing more effective cancer therapies that target cells propelling cancer growth.

Areas covered in this review: We review evidence supporting the CSC model and associated implications for understanding cancer biology and developing novel therapeutic strategies. Current controversies and unanswered questions of the CSC model are also discussed.

What the reader will gain: This review aims to describe how the CSC model is key to developing novel treatments and discusses associated shortcomings and unanswered questions.

Take home message: A fresh look at cancer biology and treatment is needed for many incurable cancers to improve clinical prognosis for patients. The CSC model posits a hierarchy in cancer where only a subset of cells drive malignancy, and if features of this model are correct, has implications for development of novel and hopefully more successful approaches to cancer therapy.

Figure 1

Cancer stem cell hypothesis. Cancer stem cells (CSCs) are organized into a hierarchy much like normal stem cells, with long-term self-renewing CSCs differentiating into cells with decreasing self-renewal potential. Clinically, tumor malignancy may be correlated to the number of CSCs, which drive tumor growth and recurrence.

Figure 2

Therapeutic relevance of cancer stem cells (CSCs). Tumors contain a mix of CSCs, progenitor-like cells, and differentiated tumor mass. Conventional therapies kill mostly progenitor-like and tumor mass cells, while therapy-resistant CSCs survive and continue to proliferate leading to recurrence. CSC-specific therapies kill or differentiate the CSCs. Without the self-renewing CSCs to drive tumor progression, the tumor shrinks and eventually dies.

Figure 3

Personalized CSC-specific therapies. Increasing evidence is revealing that drug sensitivity of CSCs may be patient as well as tumor specific, which will require personalized therapies. CSCs are isolated via surface marker or functional assays and subjected to high-throughput drug screening. The identified CSC-specific drug(s) are then administered to the patient, resulting in tumor shrinkage and death.