Deoxyribonucleic acid and associated cellular components (DNA)

Deoxyribonucleic acid (DNA) and its associated cellular components, including histones and the chromatin-remodeling machinery, constitute a primary class of therapeutic targets in modern medicine [1, 4]. In oncology, traditional cytotoxic agents such as alkylating agents and intercalators directly disrupt the DNA double helix to trigger apoptosis in rapidly proliferating cancer cells [6, 11]. Beyond direct damage, the target encompasses the complex processes of DNA replication, transcription, and repair, which are often dysregulated in disease states [2, 8]. Recent therapeutic advancements focus on the DNA damage response (DDR) pathway, employing inhibitors that exploit specific genetic vulnerabilities like BRCA mutations through synthetic lethality [5, 10]. Furthermore, epigenetic therapies target DNA-associated proteins to reprogram gene expression without altering the underlying sequence [3, 7]. Despite their clinical utility, drugs targeting DNA frequently exhibit narrow therapeutic indices and significant safety concerns, including the risk of secondary cancers and systemic toxicity to healthy tissues [11, 15].

Other names

DNADeoxyribonucleic acidChromatinGenomic DNANuclear DNAGenetic material

Drugs targeting DNA and its associated components act through several distinct mechanisms: covalent alkylation or cross-linking of DNA strands, non-covalent intercalation between base pairs, inhibition of topoisomerases to induce strand breaks, and the inhibition of DNA repair enzymes like PARP to exploit synthetic lethality [1, 6, 9]. Additionally, antimetabolites interfere with the synthesis of DNA precursors, while epigenetic agents modulate DNA methylation and histone acetylation to alter gene expression patterns [3, 5].