The present invention relates to Orexin-B polypeptides and uses thereof, in particular for the treatment of cancer. In particular, the polypeptide of the present invention comprises the amino acid sequence ranging from the amino acid residue at position 6 to the amino acid residue at position 28 in SEQ ID NO:2 wherein at least one amino acid residue position 6, 7, 8, 9, 10, 12, 13, 14, 19, 21 or 23 is substituted and the amino acid residues at position 11 15 16 17 18 20 22 24 25 26 27 and 28 are not deleted or substituted.