PIK3CA and colorectal carcinoma: Conversely, although FH loss is rare in CRC compared to renal cancer (69), its downregulation leads to fumarate accumulation (70), its downregulation leads to fumarate accumulation (70), which can activate oncogenic PI3K/AKT via PTEN succinylation (71) and stimulate HIF1A/Nrf2 pathways to fuel proliferation (72).