Prognostic, diagnostic and therapeutic value of the cancer tubulin code.

Abstract

Microtubules are essential cytoskeleton polymers composed of α/β-tubulin heterodimers that play a central role in the regulation of various cellular processes, including cell division, cell shape, cell polarity, motility and intracellular trafficking. The expression of different tubulin genes results in a variety of isotypes that, combined with post-translational modifications (PTMs), define a "tubulin code" that generates microtubule diversity. Growing evidence has shown promising links between tubulin isotypes and PTMs with several cancer properties, leading to the emergence of the concept of a "cancer tubulin code". In this review, we focus on dissecting the impact of tubulin acetylation, detyrosination and polyglutamylation on microtubule properties and functions, and how these PTMs, together with specific tubulin isotypes, affect cancer cell division, invasion and metastasis. Because conventional chemotherapy with microtubule-targeting drugs often leads to resistance and accounts for a high mortality rate among cancer patients, we discuss possible directions that explore the potential of the cancer tubulin code and respective microtubule diversity in improving drug response, while overcoming resistance. Lastly, we address the therapeutic value of small-molecule inhibitors of tubulin-modifying enzymes in cancer treatment. Overall, this review showcases the potential of exploring the cancer tubulin code to open new avenues in diagnostic, prognostic and therapeutic applications for precision oncology.