This review by Douglas Hanahan synthesizes twenty-five years of research into the hallmarks of cancer, a conceptual framework used to organize the vast complexities of the disease. The author categorizes the mechanistic foundation of cancer into four distinct dimensions: acquired functional capabilities, enabling phenotypic characteristics, specialized cells within the tumor microenvironment, and systemic interactions. The updated model identifies nine hallmark capabilities, such as sustaining proliferative signaling and evading immune destruction, alongside five enabling traits like genomic instability and chronic inflammation. A significant focus is placed on the tumor microenvironment, where diverse cell types like fibroblasts, macrophages, and neurons are reprogrammed to support malignancy. Furthermore, the text explores how systemic factors like aging and obesity modulate these hallmarks, influencing how tumors develop and evolve. Ultimately, Hanahan proposes that therapeutic co-targeting—using drug combinations to disrupt multiple hallmarks simultaneously—could overcome adaptive resistance and significantly improve patient outcomes.

References:

• Hanahan D. Hallmarks of cancer—Then and now, and beyond[J]. Cell, 2026.