Several mechanisms of intrinsic resistance have been described among whom loss of PTEN, cyclin D1 amplification, loss of NF1, RAC1 P29S mutation, HGF secretion, MAP3K8 overexpression, loss of the USP28–FBW7 complex, low levels of CD8 tumor-infiltrating T cells and increased expression of the immune inhibitory molecule PD-L1 (21–31). The gene discussed is RAC1; the disease is neoplasm.