The tumor is a main producer of factors triggering metabolic reprograming and wasting, including miRNAs, PTHrP (parathyroid hormone-related protein)106,111,112, known to cause hypercalcemia in cancer patients113, and D-2-hydroxyglutarate (D2-HG), an oncometabolite that is secreted by leukemia cells as a consequence of mutations of the TCA (tricarboxylic acid/Krebs) cycle enzymes isocitrate dehydrogenase 1 and 2. This evidence concerns the gene PTHLH and hypercalcemia disease.