Determining the capability of a test compound to affect solid tumor stem cells

A method for determining the capability of a test compound to affect the number or frequency of solid tumor stem cells of epithelial origin, the method comprising:

• a) exposing a first set of solid tumor cells of epithelial origin in a first test animal, but not a second set of the solid tumor cells in a second test animal, to a test compound, wherein the solid tumor cells comprise solid tumor stem cells;
• b) injecting unfractionated tumor cells from the first test animal at varying numbers of cells into a first series of host animals and injecting unfractionated tumor cells from the second test animal at varying numbers of cells into a second series of host animals;
• c) determining tumor formation frequency and rate in both the first and second series of host animals;
• d) determining by limiting dilution analysis the number or frequency of solid tumor stem cells in the first and second test animals based on the tumor formation frequency and rate in the first and second series of host animals, respectively;
• and
• e) comparing the number or frequency of solid tumor stem cells in the first test animal to the second test animal, wherein (i) a decrease in the number or frequency of solid tumor stem cells in the first test animal relative to the second test animal indicates the test compound is capable of decreasing the number or frequency of solid tumor stem cells, and (ii) an increase in the number or frequency of solid tumor stem cells in the first test animal relative to the second test animal indicates the test compound is capable of increasing the number or frequency of solid tumor stem cells.

A method for determining the capability of a test compound to affect the number or frequency of solid tumor stem cells of epithelial origin, the method comprising:

• a) exposing a first set of solid tumor cells of epithelial origin, but not a second set of the solid tumor cells, to a test compound, wherein the solid tumor cells comprise solid tumor stem cells;
• b) injecting the first set of solid tumor cells at varying numbers of cells into a first series of host animals and injecting the second set of solid tumor cells at varying numbers of cells into a second series of host animals, wherein the varying numbers of cells injected into the first series of host animals are equal to the varying numbers of cells injected into the second series of host animals;
• c) determining tumor formation frequency and rate in both the first and second series of host animals;
• d) determining by limiting dilution analysis the number or frequency of solid tumor stem cells in the first and second sets of solid tumor cells based on the tumor formation frequency and rate in the first and second series of host animals, respectively;
• and
• e) comparing the number or frequency of solid tumor stem cells in the first set of solid tumor cells to the second set of solid tumor cells, wherein (i) a decrease in the number or frequency of solid tumor stem cells in the first set of solid tumor cells relative to the second set indicates the test compound is capable of decreasing the number or frequency of solid tumor stem cells, and (ii) an increase in the number or frequency of solid tumor stem cells in the first set of solid tumor cells relative to the second set indicates the test compound is capable of increasing the number or frequency of solid tumor stem cells.