Chemotherapy not only enriches but also induces cancer stem cells

Cancer stem cells are regarded as the hurdle of cancer therapy at least partially due to their intrinsic resistance to therapy. To this end, chemotherapy is widely used for enrichment of cancer stem cells. In contrast to the dogma, we hypothesized that besides enrichment, cancer stem cells could also be induced by chemotherapy in those regions without sufficient drug delivery. Due to the imbalance of the angiogenesis and insufficient blood supply in certain regions of the tumor mass, chemotherapy delivery is compromised in these regions. The insufficient drug delivery in turn transforms the bulk cancer cells to stem cells rather than kill them through NFkappaB-HIF, NFkappaB-Wnt and other signals. Detection of the induction of cancer stem cells from the chemotherapy treated non-stem cancer cells would shed light on our hypothesis, which in turn would broad our understanding of clinical cancer chemotherapy.