MAP2K7 and neoplasm: In many cases, resistance is caused by reactivation of the MAPK pathway (RAS mutation, MEK and/or BRAF amplification, differential splicing leading to truncated variants of BRAF, activation of MAPKK), activation of the PI3K pathway through genetic alterations of PTEN, overexpression and activation of PDGF, IGF1, or c-Met receptors, or development of a pro-oncogenic tumor microenvironment (33–36).