The classical cancer stem cell theory (CCSCT) proposes that tumors contain
a subpopulation of rare cancer cells with stem-like properties (cancer stem cells, CSCs)
that are organized hierarchically and are responsible for chemoresistance and tumor
relapse. In this model, CSCs can generate non-CSCs, but this process is irreversible
(unidirectional model). Experimental data provided evidence that cancer cells are
extremely plastic in terms of stemness and that both CSCs and non-CSCs can
interconvert into each other. As a result, alternative models of cancer stem cell biology
such as the Stemness Phenotype Model, the Complex System Model, the Dynamic
CSC Model and the Reprogramming Model have been proposed to reconcile
experimental data with the working models of CSCs. These alternative models have
profound implications for the development of new therapeutic strategies for cancer
treatment. The aim of this chapter is to provide an overview of each of these alternative
models of CSCs, their clinical implications and to discuss potential strategies to
develop more effective therapeutic regimens for cancer treatment.
Keywords: Cancer stem cells, Clonal evolution, Chemotherapy, Microenvironment,
Plasticity, Reprogramming, Stem cell theory, Stemness, Stemness
phenotype model.
