Cancer origin in committed versus stem cells: Hypothetical antineoplastic mechanism/s associated with stem cells

It has been assumed for a long time that cancer originates in stem cells, the so-called stem cell theory of cancer origin. However, the origin of cancer in committed cells is becoming increasingly recognised. The author discusses accumulated data suggesting the preferential origin of cancer in committed cells. From histopathological, clinical and biological features, two broad tumour categories are here delineated according to the presumed cell stage of malignant transformation: common adult cancers and childhood/undifferentiated tumours corresponding to late and early stage origin, respectively. Higher cancer incidence in committed than stem cells, as well as other observations presented is consistent with the existence of an anti-cancer protective mechanism/s specific to stem cells postulated in a previous paper. Furthermore, two important carcinogenic pathways, the telomere attrition pathway and INK4a pathway, are expected to spare stem cells from direct cancer transformation. It is suggested that these two pathways are differentially involved in the two broad tumour categories delineated.