Tumor cell deoxyribonucleic acid (DNA) and nearby cellular macromolecules (DNA)

Tumor cell deoxyribonucleic acid (DNA) and nearby cellular macromolecules represent the primary site of action for many cytotoxic chemotherapies and radiopharmaceuticals. DNA serves as the essential blueprint for cellular function and replication; damaging it leads to cell cycle arrest and programmed cell death (National Cancer Institute, 2023). The inclusion of "nearby cellular macromolecules" refers to the proteins, lipids, and RNA within the nucleus or cytoplasm that are affected by reactive oxygen species (ROS) or high-energy particles emitted by radionuclides (FDA, Xofigo Label, 2013). This target is particularly relevant for alpha-emitting radiopharmaceuticals, which utilize high linear energy transfer (LET) to induce dense ionization tracks, causing complex double-strand breaks that are difficult for the cell to repair (PubMed, PMID: 28103444). While this mechanism is highly effective at eradicating tumor cells, the lack of inherent specificity for malignant versus healthy DNA often results in significant side effects, such as bone marrow suppression and the potential for secondary malignancies (StatPearls, 2023).

Other names

Genomic DNANuclear DNACellular macromoleculesChromatinTumor DNA

Induction of DNA double-strand breaks, DNA alkylation, DNA intercalation, and oxidative damage to surrounding proteins and lipids via ionizing radiation or chemical reactivity.