Compositions and methods for identifying and treating cachexia or pre-cachexia

A method of inhibiting the loss of myosin heavy chain in a myocyte, inhibiting lipolysis in an adipocyte, or inhibiting atrophy in a myocyte, adipocyte, or hepatocyte, the method comprising:

• contacting the myocyte, adipocyte, or hepatocyte with an effective amount of an agent that inhibits Receptor for Advanced Glycation Endproducts (RAGE) activity, wherein the RAGE inhibitor agent is recombinant soluble RAGE (rsRAGE), an anti-RAGE antibody, a RAGE blocking peptide that inhibits binding of RAGE to ligands, a small molecule that inhibits binding of RAGE to ligands, a dominant negative RAGE, an inhibitor of RAGE phosphorylation, an inhibitor of RAGE aggregation, or an inhibitor of RAGE interactions with other heterotypic receptors.

A method of treating pre-cachexia or preventing undesirable muscle or fat loss in a cancer patient, the method comprising

• administering to the subject an effective amount of an agent that inhibits Receptor for Advanced Glycation Endproducts (RAGE) activity, wherein the RAGE inhibitor is recombinant soluble RAGE (rsRAGE), an anti-RAGE antibody, a RAGE blocking peptide that inhibits binding of RAGE to ligands, a small molecule that inhibits binding of RAGE to ligands, a dominant negative RAGE, an inhibitor of RAGE phosphorylation, an inhibitor of RAGE aggregation, or an inhibitor of RAGE interactions with other heterotypic receptors.

A method of inhibiting the progression of pre-cachexia to cachexia, the method comprising

• administering to the subject an effective amount of an agent that inhibits Receptor for Advanced Glycation Endproducts (RAGE) activity, wherein the RAGE inhibitor is recombinant soluble RAGE (rsRAGE), an anti-RAGE antibody, a RAGE blocking peptide that inhibits binding of RAGE to ligands, a small molecule that inhibits binding of RAGE to ligands, a dominant negative RAGE, an inhibitor of RAGE phosphorylation, an inhibitor of RAGE aggregation, or an inhibitor of RAGE interactions with other heterotypic receptors.

A method of enhancing cancer sensitivity to chemotherapy, the method comprising

• administering gemcitabine in combination with an anti-RAGE therapy;
• wherein the anti-RAGE therapy comprising recombinant soluble RAGE (rsRAGE), an anti-RAGE antibody, a RAGE blocking peptide, a small molecule that inhibits binding of RAGE to ligands, a dominant negative RAGE, an inhibitor of RAGE phosphorylation, an inhibitor of RAGE aggregation, FPS1, FPS2, FPS3, FPS-ZM1, PF-04494700, or an inhibitor of RAGE interactions with other heterotypic receptors, thereby enhancing cancer sensitivity to chemotherapy.