To what extent are the "sets" of biologic properties expressed by hypoxic cancer cells and by cancer "stem" cells equivalent, intersecting, disjoint or complementary? Some implications for the design of cancer therapies.

Resistance to various cancer therapies with survival or recurrence of a malignancy has been ascribed to the inability to "kill" hypoxic cancer cells. The reported resistance of cancer "stem" cells has also been proposed as a major reason for this outcome. In planning therapy, it should be important to know whether these two categories "overlap": do "hypoxic" cells subsume cancer "stem" cells; alternately, are "stem" cells somewhat hypoxic or are these categories distinct? If the former is true and these categories overlap, to what extent do their properties share biochemical elements in common; if the latter is the case, should both properties be "targeted" independently? The inability of a proposed therapy to suppress these foci of resistance could preclude a successful outcome. Results from pre-clinical and clinical laboratory determination of the stem cell/hypoxic cell response may reflect the likely outcome of the proposed clinical treatment.