In the past two decades a small number of infrequently dividing cells have been proposed as the source of multi-drug resistance during cancer treatment. These cells identified by their expression of stem cell markers have been shown to proliferate when grafted in animals and have been called cancer stem cells in analogy to adult stem cells maintaining organ homeostasis. In this talk different kinetic models of tumor proliferation are presented and compared to tumor kinetics in large number of patients with metastatic disease obtained from cancer clinical trials. The conclusion from this analysis is that almost all analyzed tumors after initial volume decrease begin to grow exponentially, inconsistent with the hypothesis that small number of self-renewing, drug resistance cells drive this growth. Cell proliferation resembles the proliferation of embryonic stem cells early in embryogenesis and not of adult stem cells. Our data is consistent with exponential cell proliferation with fixed growth rate, implying that the number of proliferating cells in these cancers is very large and divide symmetrically. The main implication of this work is that cancer therapies must target all cells and not just a small subset of cells in a tumor.
1. To present current models of tumor growth and evidence that in advanced cancers, although rare stem-like cancer cells might exist, the majority of cells drive tumor growth.
2. For a therapy to be curative it has to target all cancer cells, because most cells are the source of drug resistance.