Tiny proteins, great impacts: non canonical ORFs in cancer

Recent advances in genomics and proteomics have unveiled noncanonical open reading frames (ncORFs) or translons (from translation regions) within regions once deemed non-coding. These ncORFs may encode functional microproteins that play pivotal roles in cancer biology, influencing tumor progression, immune responses, and therapeutic outcomes. This mini review explores the methodologies used to identify and characterize ncORF-encoded microproteins and highlights the implications of ncORF microproteins as tumor-specific antigens, regulatory molecules, and therapeutic targets, underscoring the transformative potential of ncORFs in cancer.