Gene signature for the prediction of NF-kappaB activity
Methods for predicting NF-kappaB (NF-kB) activity in a tumor, and more particularly to methods for predicting survival and therapeutic outcome, and selecting therapy in subjects with tumors, e.g., adenocarcinomas, e.g., lung adenocarcinomas and melanomas.
1. A method of selecting a treatment for a subject who has a tumor and treating the subject, the method comprising:
determining gene expression levels for GBP1, PSMB9, IRF1, TAP1, TNFAIP3, CCL5, PSMB8, IL32, SH2B3 and NFKBIE in a sample comprising cells from the tumor; and
comparing the gene expression levels to reference levels;
optionally assigning a score to the tumor based on the comparison of the gene expression levels in the tumor to the reference levels;
detecting the presence of gene expression levels above the reference levels, or a score above a threshold score, and selecting a treatment for the subject comprising administering an NF-kB inhibitor or immunotherapy; or
detecting the presence of gene expression levels below the reference levels, or a score below a threshold score;
selecting a treatment for the subject comprising administering an NF-kB activator and immunotherapy, and administering the selected treatment to the subject.
2. The method of claim 1 , wherein the tumor is an adenocarcinoma.
3. The method of claim 2 , wherein the adenocarcinoma is lung adenocarcinoma or melanoma.
4. The method of claim 1 , wherein determining gene expression levels comprises performing an assay to determine gene expression levels in the sample.
5. The method of claim 1 , wherein assigning a score to the tumor based on the comparison of the gene expression levels in the tumor to the reference levels comprises using an algorithm to calculate a score.
6. The method of claim 1 , wherein the NF-kB activator is an anticancer agent, preferably selected from the group consisting of taxanes, vinca alkaloids, and topoisomerase inhibitors.
7. The method of claim 1 , wherein the NF-kB inhibitor is selected from the group consisting of sulfasalazine, Luteolin, rapamycin, temsirolimus and everolimus, caffeic acid phenethylester, SN50, parthenolide, triptolide, wedelolactone, lactacystin, substituted resorcinols, (E)-3-(4-methylphenylsulfonyl)-2-propenenitrile, Bay 11-7082, Bay 11-7821, or Bay 11-7085, Pranlukast, etoposide, bortezomib, MLN9708, PS-1145, tetrahydrocurcuminoids, Tetrahydrocurcuminoid CG, extracts of Paulownia tomentosa wood, and MG-132 (Z-Leu-Leu-Leu-H).
8. The method of claim 1 , wherein the immunotherapy is selected from the group consisting of administration of dendritic cells or peptides with adjuvant; DNA-based vaccines; cytokines; cyclophosphamide; anti-interleukin-2R immunotoxins; and antibodies, virus-based vaccines, formulations of Toll-like Receptor or RIG-I-like receptor ligands, Adoptive T cell therapy or other cell types.
9. The method of claim 8 , wherein the antibodies are selected from the group consisting of anti-CD137, anti-PD1, anti-CD40, anti-PDLL, and anti-CTLA-4 antibodies.