Targeting transposable elements in cancer: developments and opportunities

Abstract

Transposable elements (TEs), comprising nearly 50% of the human genome, have transitioned from being perceived as “genomic junk” to key players in cancer progression. Contemporary research links TE regulatory disruptions with cancer development, underscoring their therapeutic potential. Advances in long-read sequencing, computational analytics, single-cell sequencing, proteomics, and CRISPR-Cas9 technologies have enriched our understanding of TEs' clinical implications, notably their impact on genome architecture, gene regulation, and evolutionary processes. In cancer, TEs, including long interspersed element-1 (LINE-1), Alus, and long terminal repeat (LTR) elements, demonstrate altered patterns, influencing both tumorigenic and tumor-suppressive mechanisms. TE-derived nucleic acids and tumor antigens play critical roles in tumor immunity, bridging innate and adaptive responses. Given their central role in oncology, TE-targeted therapies, particularly through reverse transcriptase inhibitors and epigenetic modulators, represent a novel avenue in cancer treatment. Combining these TE-focused strategies with existing chemotherapy or immunotherapy regimens could enhance efficacy and offer a new dimension in cancer treatment. This review delves into recent TE detection advancements, explores their multifaceted roles in tumorigenesis and immune regulation, discusses emerging diagnostic and therapeutic approaches centered on TEs, and anticipates future directions in cancer research.