In this neo-Darwinian process, the strong negative selective pressure by adaptive immune surveillance mechanisms against emerging primary cancers can result in the selection of tumour variants that have lost the expression of APM genes, rendering subsequent metastasis invisible to recognition by host T lymphocytes (Jefferies et al., 1993a; Gabathuler et al., 1994; Alimonti et al., 2000; Shankaran et al., 2001; Setiadi et al., 2007a; Saranchova et al., 2018; Tang et al., 2020; Dhatchinamoorthy et al., 2021a). The gene discussed is ANPEP; the disease is neoplasm.