Chemotherapeutic drug screening in 3D-Bioengineered human myobundles provides insight into taxane-induced myotoxicities.
| dc.contributor.author | Torres, Maria J | |
| dc.contributor.author | Zhang, Xu | |
| dc.contributor.author | Slentz, Dorothy H | |
| dc.contributor.author | Koves, Timothy R | |
| dc.contributor.author | Patel, Hailee | |
| dc.contributor.author | Truskey, George A | |
| dc.contributor.author | Muoio, Deborah M | |
| dc.date.accessioned | 2022-11-07T14:21:10Z | |
| dc.date.available | 2022-11-07T14:21:10Z | |
| dc.date.issued | 2022-10 | |
| dc.date.updated | 2022-11-07T14:21:00Z | |
| dc.description.abstract | 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. | |
| dc.identifier | S2589-0042(22)01461-4 | |
| dc.identifier.issn | 2589-0042 | |
| dc.identifier.issn | 2589-0042 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Elsevier BV | |
| dc.relation.ispartof | iScience | |
| dc.relation.isversionof | 10.1016/j.isci.2022.105189 | |
| dc.subject | Bioengineering | |
| dc.subject | Biological sciences | |
| dc.subject | Cancer | |
| dc.subject | Pharmacology | |
| dc.title | Chemotherapeutic drug screening in 3D-Bioengineered human myobundles provides insight into taxane-induced myotoxicities. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Koves, Timothy R|0000-0001-8763-5866 | |
| duke.contributor.orcid | Truskey, George A|0000-0002-6885-4489 | |
| duke.contributor.orcid | Muoio, Deborah M|0000-0003-3760-9277 | |
| pubs.begin-page | 105189 | |
| pubs.issue | 10 | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Pratt School of Engineering | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Basic Science Departments | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.organisational-group | Institutes and Centers | |
| pubs.organisational-group | Pharmacology & Cancer Biology | |
| pubs.organisational-group | Biomedical Engineering | |
| pubs.organisational-group | Medicine | |
| pubs.organisational-group | Medicine, Endocrinology, Metabolism, and Nutrition | |
| pubs.organisational-group | Medicine, Geriatrics | |
| pubs.organisational-group | Duke Cancer Institute | |
| pubs.organisational-group | Institutes and Provost's Academic Units | |
| pubs.organisational-group | University Institutes and Centers | |
| pubs.organisational-group | Duke Molecular Physiology Institute | |
| pubs.organisational-group | Sarah Stedman Nutrition & Metabolism Center | |
| pubs.organisational-group | Center for the Study of Aging and Human Development | |
| pubs.organisational-group | Initiatives | |
| pubs.organisational-group | Duke Science & Society | |
| pubs.organisational-group | Nicholas Institute-Energy Initiative | |
| pubs.organisational-group | Regeneration Next Initiative | |
| pubs.publication-status | Published | |
| pubs.volume | 25 |
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