Microtubule dynamics and DNA replication

Microtubule dynamics and DNA replication are fundamental biological processes rather than a single molecular target. Microtubule dynamics involve the continuous assembly and disassembly of tubulin polymers, which is essential for maintaining cell shape, intracellular transport, and the formation of the mitotic spindle during cell division (Jordan & Wilson, 2004). DNA replication is the high-fidelity duplication of the cellular genome, a prerequisite for cell division (Bell & Dutta, 2002). In oncology, these processes are primary targets for cytotoxic chemotherapy. For instance, taxanes and vinca alkaloids modulate microtubule stability to induce mitotic arrest, while antimetabolites and platinum-based agents interfere with DNA synthesis and repair (Perez, 2009). Because these processes are central to the proliferation of both malignant and healthy rapidly-dividing cells, drugs targeting them often result in side effects like myelosuppression and neuropathy (Argyriou et al., 2012). Consequently, while highly effective in reducing tumor burden, these mechanisms lack the specificity of modern targeted therapies directed at unique oncogenic drivers. These processes are often evaluated together in the context of cell cycle inhibitors that act at different phases, specifically the S-phase for DNA replication and the M-phase for microtubule-dependent mitosis.

Other names

Cell cycle inhibitionCytotoxic chemotherapy targetsMitosis and DNA synthesisCell cycle progression

Inhibition of tubulin polymerization or depolymerization to disrupt the mitotic spindle, and interference with DNA polymerase activity or DNA structural integrity to halt genome duplication (Jordan & Wilson, 2004; Bell & Dutta, 2002).