This blocking leads to the inhibition of EGFR downstream signaling pathways, including the RAF/MEK/ERK pathway, which is mainly involved in cell proliferation, and the PI3K/AKT pathway, which is mainly involved in cell survival and tumor invasion.8,9 However, once point mutations in the KRAS oncogene occur, the downstream pathways become constitutively active (RAF/MEK/ERK, SAPK/JNK, and possibly PI3K/AKT pathways).10 This constitutive activity is considered the major reason that mutant KRAS CRCs are resistant to anti-EGFR therapy.1,7. The gene discussed is EGFR; the disease is neoplasm.