PTEN and neoplasm: Several important tumor-intrinsic pathways are associated with primary and adaptive resistance including (1) the mitogen-activated protein kinase (MAPK) pathway and/or loss of phosphatase and tensin homolog (PTEN) expression, which enhances PI3K signaling, (2) expression of WNT/β-catenin signaling pathway, (3) loss of interferon-gamma (IFNγ) signaling pathways, and (4) loss of tumor antigen expression (Figure 1B) [25].