Microtubule dynamics in cancer metastasis: Harnessing the underappreciated potential for therapeutic interventions

Abstract

Microtubules, dynamic cytoskeletal structures crucial for cellular processes, have surfaced as promising targets for cancer therapy owing to their pivotal role in cancer progression and metastasis. This review comprehensively explores the multifaceted landscape of microtubule-targeting drugs and their potential to inihibit cancer metastasis. Although the role of Actin cytoskeleton is well known in controlling metastasis, only recently Microtubules are emerging as a potential controller of metastasis. We delve into the processes at the core of antimetastatic impacts of microtubule-targeting agents, both through direct modulation of microtubules and via alternative pathways. Drawing from in vitro and in vivo studies, we analyze the cytotoxic and antimetastatic doses of various compounds, shedding light on their therapeutic potential. Furthermore, we discuss the emerging class of microtubule targeting drugs, and their role in metastasis inhibition, such as microtubules acetylation inhibitory drugs, particularly histone deacetylase inihibitors and antibody-drug conjugates. Histone deacetylase (HDAC) strengthens the microtubule cytoskeleton through acetylation. Recently, HDAC inhibitors have been discovered to have antimetastatic properties. Here, the role of HDAC inhibitors in stopping metastasis is discussed with respect to microtubule cytoskeleton. Surprisingly, novel antibody conjugates of microtubule-targeting agents, which are in clinical trials, were found to be antimetastatic. This review discusses these antibody conjugates in detail. Additionally, we elucidate the intricate crosstalk between microtubules and other cytoskeletal proteins, unveiling novel therapeutic strategies for metastasis suppression. By providing a wide-ranging overview of the complex interplay between microtubules and cancer metastasis, this review contributes to the comprehension of cancer's biological mechanisms and the development of innovative therapeutic interventions to mitigate metastatic progression.