Data mined from The Cancer Genome Atlas (TCGA) indicates that genomic alterations in the RAS/MAPK signaling pathway, including mutations in KRAS, NRAS, and BRAF, as well as in the PI3K/AKT pathway, such as PIK3CA mutations, are among the most frequent in colorectal cancer (CRC), collectively occurring in over 50% of cases [48,75,76], and the MAP2K1-K57N alteration all contribute significantly to driving tumor progression and therapy resistance [77,78]. The gene discussed is PIK3CA; the disease is colorectal cancer.