A method of treating melanoma in a subject by restoring the subject's melanoma cells' sensitivity to retinoic acid (RA), comprising administering to the subject i) prostaglandin D2 (PGD2) or a prostaglandin D2 (PGD2) receptor agonist and ii) retinoic acid (RA) or a retinoic acid receptor (RAR) agonist, wherein the prostaglandin D2 (PGD2) or the prostaglandin D2 (PGD2) receptor agonist is in an amount sufficient to increase SOX9 expression in the subject, thus restoring the subject's melanoma cells' sensitivity to retinoic acid (RA) or the retinoic acid receptor (RAR) agonist, and wherein the retinoic acid (RA) or retinoic acid receptor (RAR) agonist is in an amount sufficient, in combination with the prostaglandin D2 (PGD2) or the prostaglandin D2 (PGD2) receptor agonist, to induce proliferation arrest, differentiation, or apoptosis of melanoma cells, thus treating melanoma in the subject.