Here, we took advantage of four low-passage CRC cell lines with well-defined molecular phenotypes [29, 30] to evaluate the biological and molecular effects of selected SMI that interfere with signaling through two key mitogenic/antiapoptotic pathways in CRC cells, RAS/RAF/MEK/ERK, and PTEN/PI3K/AKT/mTOR. This evidence concerns the gene PIK3CA and colorectal carcinoma.