PIK3CA and neoplasm: Mutations and amplifications in signaling genes PDGFRA, PIK3CA/PIK3R1, FGFR, EGFR and ACVR1 coupled with the loss of function of tumor suppressors genes TP53 and PTEN combine with hallmark instigating H3-alterations (H3–3A, H3C2/H3C3, EZHIP) to drive a highly clonal disease, limiting the benefit of single agents [4, 5].