Alterations in signaling molecules in the HER receptor family of signaling pathways, e.g., deletion of the tumor suppressor genes inositol polyphosphate 4-phosphatase type II (INPP4B) and phosphatase and tensin homologue (PTEN), are also known to actuate the PI3K pathway.[68] These alternative or cross-talk mechanisms that activate the HER signaling pathway network could partially explain the resistance to treatment targeting only HER2. This evidence concerns the gene PIK3CD and neoplasm.