Activation of either the PI3K-Akt-mTOR or Ras-Raf-MEK-ERK signaling axis was shown to induce COX-2 expression in a variety of tumors; overexpression of COX-2 by HIF-1α induction further increased tumor cell proliferation, angiogenesis, drug resistance, and decreased apoptosis [43,52]. This evidence concerns the gene RAF1 and neoplasm.