ERBB2 and neoplasm: Indeed, our data analysis of ERBB2-positive tumors in The Cancer Genome Atlas revealed amplification and/or missense mutations in the ERBB2 signal pathway downstream genes NFKBIE, PTK2, and PIK3CA. Being downstream of, and thus bypassing, the therapeutic target, represents one mechanism of cell survival that can lead to drug resistance and tumor relapse, possibly requiring additional therapies.