The role of HMGA1 in genome stability: Implications in human cancer

High mobility group A1 (HMGA1), a non-histone chromatin structural protein encoded by the HMGA1 gene, plays a critical role in cancer. Recent studies have increasingly focused on its functions in genomic stability and cell death, revealing its involvement in tumorigenesis, cancer progression, and chemotherapy resistance. Consequently, inhibiting HMGA1 represents a promising strategy for developing novel cancer therapies. This review summarizes the cellular and molecular functions of HMGA1 in regulating genomic integrity and cell death in cancer. Furthermore, we discuss current HMGA1-targeting strategies, with emphasis on approaches leveraging its structural and functional characteristics, aiming to provide new insights for future research on HMGA1-targeted cancer therapies.