At the nucleus of cancer: how the nuclear envelope controls tumor progression

Historically considered downstream effects of tumorigenesis-arising from changes in DNA content or chromatin organization-nuclear alterations have long been seen as mere prognostic markers within a genome-centric model of cancer. However, recent findings have placed the nuclear envelope (NE) at the forefront of tumor progression, highlighting its active role in mediating cellular responses to mechanical forces. Despite significant progress, the precise interplay between NE components and cancer progression remains under debate. In this review, we provide a comprehensive and up-to-date overview of how changes in NE composition affect nuclear mechanics and facilitate malignant transformation, grounded in the latest molecular and functional studies. We also review recent research that uses advanced technologies, including artificial intelligence, to predict malignancy risk and treatment outcomes by analyzing nuclear morphology. Finally, we discuss how progress in understanding nuclear mechanics has paved the way for mechanotherapy-a promising cancer treatment approach that exploits the mechanical differences between cancerous and healthy cells. Shifting the perspective on NE alterations from mere diagnostic markers to potential therapeutic targets, this review calls for further investigation into the evolving role of the NE in cancer, highlighting the potential for innovative strategies to transform conventional cancer therapies.