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Chemotherapeutic drug screening in 3D-Bioengineered human myobundles provides insight into taxane-induced myotoxicities.

Publication ,  Journal Article
Torres, MJ; Zhang, X; Slentz, DH; Koves, TR; Patel, H; Truskey, GA; Muoio, DM
Published in: iScience
October 21, 2022

Two prominent frontline breast cancer (BC) chemotherapies commonly used in combination, doxorubicin (DOX) and docetaxel (TAX), are associated with long-lasting cardiometabolic and musculoskeletal side effects. Whereas DOX has been linked to mitochondrial dysfunction, mechanisms underlying TAX-induced myotoxicities remain uncertain. Here, the metabolic and functional consequences of TAX ± DOX were investigated using a 3D-bioengineered model of adult human muscle and a drug dosing regimen designed to resemble in vivo pharmacokinetics. DOX potently reduced mitochondrial respiratory capacity, 3D-myobundle size, and contractile force, whereas TAX-induced acetylation and remodeling of the microtubule network led to perturbations in glucose uptake, mitochondrial respiratory sensitivity, and kinetics of fatigue, without compromising tetanic force generation. These findings suggest TAX-induced remodeling of the microtubule network disrupts glucose transport and respiratory control in skeletal muscle and thereby have important clinical implications related to the cardiometabolic health and quality of life of BC patients and survivors.

Duke Scholars

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Published In

iScience

DOI

EISSN

2589-0042

Publication Date

October 21, 2022

Volume

25

Issue

10

Start / End Page

105189

Location

United States
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Torres, M. J., Zhang, X., Slentz, D. H., Koves, T. R., Patel, H., Truskey, G. A., & Muoio, D. M. (2022). Chemotherapeutic drug screening in 3D-Bioengineered human myobundles provides insight into taxane-induced myotoxicities. IScience, 25(10), 105189. https://doi.org/10.1016/j.isci.2022.105189
Torres, Maria J., Xu Zhang, Dorothy H. Slentz, Timothy R. Koves, Hailee Patel, George A. Truskey, and Deborah M. Muoio. “Chemotherapeutic drug screening in 3D-Bioengineered human myobundles provides insight into taxane-induced myotoxicities.IScience 25, no. 10 (October 21, 2022): 105189. https://doi.org/10.1016/j.isci.2022.105189.
Torres MJ, Zhang X, Slentz DH, Koves TR, Patel H, Truskey GA, et al. Chemotherapeutic drug screening in 3D-Bioengineered human myobundles provides insight into taxane-induced myotoxicities. iScience. 2022 Oct 21;25(10):105189.
Torres, Maria J., et al. “Chemotherapeutic drug screening in 3D-Bioengineered human myobundles provides insight into taxane-induced myotoxicities.IScience, vol. 25, no. 10, Oct. 2022, p. 105189. Pubmed, doi:10.1016/j.isci.2022.105189.
Torres MJ, Zhang X, Slentz DH, Koves TR, Patel H, Truskey GA, Muoio DM. Chemotherapeutic drug screening in 3D-Bioengineered human myobundles provides insight into taxane-induced myotoxicities. iScience. 2022 Oct 21;25(10):105189.
Journal cover image

Published In

iScience

DOI

EISSN

2589-0042

Publication Date

October 21, 2022

Volume

25

Issue

10

Start / End Page

105189

Location

United States