Unmasked: transposable elements as drivers and targets in cancer

Transposable elements (TEs) – long considered ‘junk DNA’ – challenge the binary of threat and therapeutic opportunity in cancer. Their reactivation is not a singular event but a convergence of evolutionary legacy, regulatory disruption, and technological insight. This review synthesizes a growing body of work that positions TEs as both catalysts and antagonists of the tumor state. Across regulatory control, viral mimicry, protein-coding potential, and antigen presentation, TEs blur the line between harm and utility. Each example reflects a broader theme: context defines consequence. By tracing historical shifts and technological advances, we argue for an integrated view: one where TEs are not just anomalies, but dynamic agents in the complexity of cancer.