Deoxyribonucleic acid (DNA) and intracellular macromolecules (DNA)

Cellular DNA and other intracellular macromolecules represent a broad class of therapeutic targets primarily utilized in cytotoxic chemotherapy for cancer [1]. These targets are essential for the storage and transmission of genetic information, and their integrity is critical for cell survival and division [2]. Drugs targeting these molecules, such as alkylating agents and platinum-based compounds, work by forming covalent bonds or physical obstructions that prevent DNA replication and transcription [2][3]. Because these agents preferentially affect proliferating cells, they are effective against rapidly growing tumors but also impact healthy tissues with high turnover rates, such as bone marrow and the gastrointestinal lining [1][4]. This lack of specificity results in a narrow therapeutic index and significant side effects, though these treatments remain foundational in many oncology regimens [3]. Intracellular macromolecules like proteins and RNA can also be secondary targets for these reactive agents, further disrupting cellular homeostasis [2]. The resulting DNA damage triggers complex signaling pathways, including the p53-mediated response, which can lead to permanent cell cycle arrest or apoptosis [4]. Despite the rise of targeted therapies, DNA-damaging agents continue to be used in combination therapies to overcome resistance and improve patient outcomes [1].

Other names

Genomic DNANuclear DNACellular macromoleculesIntracellular proteins and nucleic acids

Drugs targeting these macromolecules typically act by inducing DNA damage through alkylation, cross-linking, or intercalation, which inhibits DNA replication and RNA transcription, leading to cell cycle arrest and apoptosis [1][2].