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Tubulin beta chain (β-tubulin) is a fundamental structural protein that dimerizes with alpha-tubulin to form microtubules, which are dynamic cytoskeletal filaments essential for cell architecture, intracellular trafficking, and the formation of the mitotic spindle [1][2]. In the context of oncology, microtubules are a validated therapeutic target because their dynamic instability is required for successful chromosome segregation during mitosis; disrupting this process leads to cell cycle arrest and apoptosis [3]. Drugs targeting β-tubulin are broadly classified into microtubule-stabilizing agents, such as taxanes, and microtubule-destabilizing agents, such as vinca alkaloids and colchicine [4]. While highly effective in treating various malignancies and inflammatory conditions like gout, these agents often face challenges such as drug resistance—frequently mediated by the overexpression of specific isotypes like TUBB3—and significant off-target toxicities [5]. Most notably, peripheral neuropathy occurs due to the disruption of microtubule-dependent axonal transport in neurons [6].
Drugs targeting beta-tubulin primarily act by modulating microtubule dynamics; microtubule-stabilizing agents (e.g., taxanes) bind to the tubulin polymer to prevent depolymerization, while microtubule-destabilizing agents (e.g., vinca alkaloids) bind to tubulin dimers to inhibit their assembly into microtubules, both of which lead to cell cycle arrest at the G2/M phase and subsequent apoptosis [3][4].
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