In the future, it would be of interest to investigate associations with other molecular markers linked to poor therapeutic responses and outcomes, which include mutations in drivers of proliferative signalling pathways, such as KRAS, SMAD4 and FGFR2 and EPHA2, which may provide means for cancer cells to become independent of paracrine signalling (Wang et al., 2022; Boerner et al., 2021). This evidence concerns the gene SMAD4 and cancer.