Several preclinical studies note the importance of the PI3 K/PTEN/AKT pathway in determining the sensitivity of CRC cell lines to cetuximab. PI3KCA mutations, present in 10–25% of CRCs [28, 39–41], have been reported to be “gain of function” mutations activating the PI3 K/AKT pathway. PIK3CA mutations, which are located in exon 9 or exon 20, can coincide with KRAS and BRAF mutations [42] and exert different oncogenic effects including resistance to anti-EGFR therapies. Here, EGFR is linked to colorectal carcinoma.