Microtubuletargeting

Microtubule targeting refers to strategies that modulate microtubule dynamics by interacting with tubulin or microtubules themselves, altering polymerization and stability to influence cellular processes such as mitosis and intracellular transport. These approaches are used in basic research and in medicine, particularly for cancer therapy.

In cells, microtubules are dynamic polymers of alpha- and beta-tubulin that exhibit dynamic instability, driven by GTP hydrolysis at the growing plus end. They form the mitotic spindle and serve as tracks for motor proteins like kinesin and dynein, enabling chromosome segregation, organelle movement, and intracellular transport.

Two major classes of microtubule-targeting agents exist in medicine. Microtubule-stabilizing agents, such as the taxanes (paclitaxel, docetaxel), bind beta-tubulin and suppress depolymerization, locking microtubules in a stable state. Microtubule-destabilizing agents, including vinca alkaloids (vincristine, vinblastine) and colchicine-site drugs, inhibit polymerization. By disrupting microtubule dynamics, these agents impair mitotic spindle function and induce cell death, particularly in rapidly dividing cells.

Clinically, MTAs are employed primarily in cancer therapy to halt cell division and trigger apoptosis. Common adverse effects include neuropathy, myelosuppression, and mucosal toxicities. Tumor resistance can arise via changes in tubulin isotypes, overexpression of drug efflux pumps, or mutations at drug-binding sites, prompting combination regimens and the development of new delivery methods and formulations.

Research on microtubule targeting aims to improve selectivity and overcome resistance, including isoform- or site-specific agents and targeted delivery systems. Additional work explores repurposing MTAs for non-cancer indications and refining strategies to balance anticancer efficacy with toxicity.