Therapeutic and diagnostic methods relating to cancer stem cells
The present invention relates in part to the discovery of genes that are deregulated in cancer stem cells (e.g., melanoma stem cells). In some aspects, methods for treating individuals having melanoma are provided; the methods involve modulating (e.g., inducing, inhibiting, etc.) the activity of the cancer stem cell associated genes. In other aspects, cell surface genes that are upregulated in melanoma stem cells are targeted for the selective isolation, detection, and killing of cancer stem cells in melanoma. Other aspects of the invention relate to reagents, arrays, compositions, and kits that are useful for diagnosing and treating melanoma.
1. A method of treating melanoma in an individual, comprising:
isolating an ATP binding cassette subfamily B member 5 (ABCB5)+ stem cell sample from the individual having melanoma,
determining an expression level of a cancer stem cell (CSC)-associated gene in the ABCB5+ stem cell sample of an individual, wherein the CSC-associated gene is programmed cell death protein 1 (PD-1);
comparing the expression level of the CSC-associated gene to a reference value and
administering to the individual a PD-1 antibody, wherein the PD-1 antibody binds to PD-1 on the surface of the ABCB5+ cancer stem cell and inhibits ABCB5+ cancer stem cell activity in order to treat the cancer based on a higher level of PD-1 expression in the ABCB5+ stem cell relative to expression levels in a ABCB5 (−) cancer bulk populations.
2. The method of claim 1 , wherein the determining step comprises detecting in the ABCB5+ stem cell sample a mRNA that is encoded by the CSC-associated gene.
3. The method of claim 1 , wherein the determining step comprises detecting in the ABCB5+ stem cell sample a polypeptide that is encoded by the CSC-associated gene.
4. The method of claim 3 , wherein the expression level of the CSC-associated gene in the ABCB5+ stem cell is at least 10% higher than the expression level of the CSC-associated gene in the ABCB5(−) cancer bulk populations.
5. The method of claim 1 , wherein the administration of PD-1 antibody to the individual affected by melanoma is intravenously.