In breast cancer cells, hypoxia also triggers alternative BRCA1-IRIS splicing in hypoxic/necrotic niches, promoting tumour progression by de-regulating wtBRCA1 function [243–247], and also inactivates TP53, ATR, BRCA2 and Bax tumour suppressors by promoting alternative intronic retention splicing and NMD, reducing TP53, ATR and BRCA2 involvement in the DNA damage response [56]. This evidence concerns the gene BAX and breast carcinoma.