Next, to assess the importance of MDK expression on rapamycin resistance in vitro and in vivo, we used an MDK inhibitor (iMDK) that specifically inhibits MDK but not other growth factors such as VEGF or pleiotrophin (PTN) (homologous to MDK)79 and was shown to potently inhibit MDK and thus enhance PD-1 therapy in melanoma mouse models80. This evidence concerns the gene MDK and melanoma.