Microproteins in cancer: identification, biological functions, and clinical implications

HighlightsMicroproteins, historically overlooked, are emerging as key players in cancer biology.Advances in genomics and proteomics enable systematic identification of cancer-associated microproteins.Microproteins contribute to cancer pathogenesis, are an important source of cryptic cancer antigens, and may offer novel therapeutic targets.Harnessing the potential of microproteins could revolutionize cancer diagnostics, therapeutics, and immunotherapy.AbstractCancer continues to be a major global health challenge, accounting for 10 million deaths annually worldwide. Since the inception of genome-wide cancer sequencing studies 20 years ago, a core set of ~700 oncogenes and tumor suppressor genes has become the basis for cancer research. However, this research has been based largely on an understanding that the human genome encodes ~19 500 protein-coding genes. Complementing this genomic landscape, recent advances have described numerous microproteins which are now poised to redefine our understanding of oncogenic processes and open new avenues for therapeutic intervention. This review explores the emerging evidence for microprotein involvement in cancer mechanisms and discusses potential therapeutic applications, with an emphasis on highlighting recent advances in the field.