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Review
. 2020 Aug;8(4):e00616.
doi: 10.1002/prp2.616.

Introducing variability in targeting the microtubules: Review of current mechanisms and future directions in colchicine therapy

Esther Forkosh  1 , Ariel Kenig  1 , Yaron Ilan  1
Affiliations
Review

Introducing variability in targeting the microtubules: Review of current mechanisms and future directions in colchicine therapy

Esther Forkosh et al. Pharmacol Res Perspect. 2020 Aug.

Abstract

Microtubules (MTs) are highly dynamic polymers that constitute the cellular cytoskeleton and play a role in multiple cellular functions. Variability characterizes biological systems and is considered a part of the normal function of cells and organs. Variability contributes to cell plasticity and is a mechanism for overcoming errors in cellular level assembly and function, and potentially the whole organ level. Dynamic instability is a feature of biological variability that characterizes the function of MTs. The dynamic behavior of MTs constitutes the basis for multiple biological processes that contribute to cellular plasticity and the timing of cell signaling. Colchicine is a MT-modifying drug that exerts anti-inflammatory and anti-cancer effects. This review discusses some of the functions of colchicine and presents a platform for introducing variability while targeting MTs in intestinal cells, the microbiome, the gut, and the systemic immune system. This platform can be used for implementing novel therapies, improving response to chronic MT-based therapies, overcoming drug resistance, exerting gut-based systemic immune responses, and generating patient-tailored dynamic therapeutic regimens.

Keywords: Inflammation; colchicine; fibrosis; microtubules; variability.

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Conflict of interest statement

YI is the founder of Oberon Sciences and is a consultant for Teva, ENZO, Protalix, Betalin Therapeutics, Immuron, SciM, Natural Shield, Tiziana Pharma, Plantylight, and Exalenz Bioscience.

Figures

FIGURE 1
FIGURE 1
A schematic presentation of a platform comprising MTs in cells of the gut wall, the microbiome, and the intestine and systemic immune systems. Introducing variability in the dosing and intervals of administration of low nonabsorbable dose of colchicine is presented as a method for targeting this platform. Quantifying cellular and whole‐organs variability patterns as well as chronobiology‐based signatures are being implemented into the drug regimens
See this image and copyright information in PMC

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