Extracellular DNA in necrotic tumor tissue (ecDNA)

Extracellular DNA (ecDNA) in necrotic tumor tissue represents a distinct molecular target found within the core of solid tumors where rapid proliferation leads to hypoxia and subsequent cell death (Chen et al., 1989, Cancer Res.). During necrosis, the loss of cell membrane integrity results in the release of genomic DNA and histones into the extracellular space, where they form stable complexes that are not readily cleared due to impaired vascular and lymphatic drainage (Epstein et al., 1988, Cancer Res.). This accumulation of ecDNA serves as a specific marker for necrotic regions, which are characteristic of many aggressive cancers. Therapeutic strategies, such as Tumor Necrosis Therapy (TNT), utilize monoclonal antibodies or fusion proteins designed to bind with high affinity to these exposed nucleic acids (Heery et al., 2015, J. ImmunoTher. Cancer). By targeting ecDNA, these agents can deliver concentrated doses of radionuclides or immunomodulatory cytokines directly to the tumor microenvironment, bypassing the need for cell-surface antigen expression. Furthermore, ecDNA acts as a damage-associated molecular pattern (DAMP), potentially stimulating the innate immune system through pathways like cGAS-STING, although its primary clinical utility remains its role as a localized anchor for targeted drug delivery (Huang et al., 2021, Front. Immunol.).

Other names

Necrotic DNACell-free DNA (cfDNA)Tumor-associated extracellular DNADNA-histone complexExtracellular genomic DNA

Binding to exposed DNA or DNA-histone complexes in necrotic regions to deliver therapeutic payloads such as cytokines or radionuclides.