The identification of a fraction of cancer stem cells (CSCs) associated with resistance to chemotherapy in most solid tumors leads to the dogma that eliminating this fraction will cure cancer. Experimental data has challenged this simplistic and optimistic model. Opposite to the classical cancer stem cell model, we introduced the stemness phenotype model (SPM), which proposed that all glioma cells possess stem cell properties and that the stemness is modulated by the microenvironment. A key prediction of the SPM is that to cure gliomas all gliomas cells (CSCs and non-CSCs) should be eliminated at once. Other theories closely resembling the SPM and its predictions have recently been proposed, suggesting that the SPM may be a useful model for other type of tumors. Here, we review data from other tumors that strongly support the concepts of the SPM applied to gliomas. We include data related to: (1) the presence of a rare but constant fraction of CSCs in established cancer cell lines, (2) the clonal origin of cancer, (3) the symmetrical division, (4) the ability of “non-CSCs” to generate “CSCs,” and (5) the effect of the microenvironment on cancer stemness. The aforenamed issues that decisively supported the SPM proposed for gliomas can also be applied to breast, lung, prostate cancer, and melanoma and perhaps other tumors in general. If the glioma SPM is correct and can be extrapolated to other types of cancer, it will have profound implications in the development of novel modalities for cancer treatment. 1. Introduction The identification of putative cancer stem cells (CSCs) in tumors some years ago gave rise to new concepts in cancer biology, and consequently new dogmas in the cancer field were established. The classical cancer stem cells model (CSM) proposes that all cancer types have a subpopulation of cancer stem cell responsible for resistance to chemo- and/or radiotherapy, concluding that eliminating this subpopulation of CSCs will cure cancer [1–5]. However, there is no consensus among experimental data regarding key issues that are important for the establishment of effective treatments. For instance, the percentage of cancer stem cells detected in glioma cell lines tumors varies from less than 1% to 100% (for review see [6]). The differences have also been observed in other types of cancer (see below). However, these discrepancies, which might be well due to differences in methodology and criteria used to detect and characterize these cells have important clinical consequences. If the percentage of CSCs is rare (<1%), the elimination (if
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