Benetatos Leonidas, Hatzimichael Eleftheria, Kapsali Eleni
Department of Hematology, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, 45500, Greece.
Mol Biol Rep. 2025 Apr 11;52(1):386. doi: 10.1007/s11033-025-10497-0.
MYC is an important transcription factor involved in physiological processes such as cell growth, proliferation and differentiation. However, aberrant MYC expression has oncogenic-driving potential and is observed in the majority of human cancers. XPO1 is a member of the exportin family of proteins which regulate protein and RNA export from the nucleus to the cytoplasm. XPO1 is aberrantly expressed in cancer, especially with the advancing of the disease. XPO1 inhibition is able to decrease MYC levels through various pathways leading to decreased cancer cell viability. These pathways include other undruggable targets such as p53 and KRAS, DNA damage repair proteins, immune response mediators including IκB, and other transcription factors such as eIF4E. Herein, we describe the potential pathways and mechanisms through which XPO1 inhibition promotes MYC downregulation and subsequent downregulation of its targets. We also describe possible drug combinations with potential clinical applications.
MYC是一种重要的转录因子，参与细胞生长、增殖和分化等生理过程。然而，MYC的异常表达具有致癌驱动潜力，在大多数人类癌症中都有观察到。XPO1是蛋白质输出蛋白家族的成员，该家族调节蛋白质和RNA从细胞核到细胞质的输出。XPO1在癌症中异常表达，尤其是随着疾病的进展。抑制XPO1能够通过各种途径降低MYC水平，从而导致癌细胞活力下降。这些途径包括其他难以成药的靶点，如p53和KRAS、DNA损伤修复蛋白、包括IκB在内的免疫反应介质，以及其他转录因子，如eIF4E。在此，我们描述了抑制XPO1促进MYC下调及其后续靶点下调的潜在途径和机制。我们还描述了可能具有潜在临床应用的药物组合。
