Journal article
Oral Carbon Monoxide Enhances Autophagy Modulation in Prostate, Pancreatic, and Lung Cancers
Advanced science, Vol.11(9), 2308346
03/06/2024
DOI: 10.1002/advs.202308346
PMCID: PMC10916612
PMID: 38084435
Appears in UI Libraries Support Open Access
Abstract
Modulation of autophagy, specifically its inhibition, stands to transform the capacity to effectively treat a broad range of cancers. However, the clinical efficacy of autophagy inhibitors has been inconsistent. To delineate clinical and epidemiological features associated with autophagy inhibition and a positive oncological clinical response, a retrospective analysis of patients is conducted treated with hydroxychloroquine, a known autophagy inhibitor. A direct correlation between smoking status and inhibition of autophagy with hydroxychloroquine is identified. Recognizing that smoking is associated with elevated circulating levels of carbon monoxide (CO), it is hypothesized that supplemental CO can amplify autophagy inhibition. A novel, gas-entrapping material containing CO in a pre-clinical model is applied and demonstrated that CO can dramatically increase the cytotoxicity of autophagy inhibitors and significantly inhibit the growth of tumors when used in combination. These data support the notion that safe, therapeutic levels of CO can markedly enhance the efficacy of autophagy inhibitors, opening a promising new frontier in the quest to improve cancer therapies.
Details
- Title: Subtitle
- Oral Carbon Monoxide Enhances Autophagy Modulation in Prostate, Pancreatic, and Lung Cancers
- Creators
- Jianling Bi - University of IowaEmily Witt - University of IowaMegan K McGovern - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, 52242, USAArielle B Cafi - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, 52242, USALauren L Rosenstock - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, 52242, USAAnna B Pearson - University of North Carolina WilmingtonTimothy J Brown - The University of Texas Southwestern Medical CenterThomas B Karasic - University of PennsylvaniaLucas C Absler - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, 52242, USASrija Machkanti - Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USAHannah Boyce - Massachusetts Institute of TechnologyDavid Gallo - Beth Israel Deaconess Medical CenterSarah L Becker - University of PortlandKeiko Ishida - Massachusetts Institute of TechnologyJoshua Jenkins - Massachusetts Institute of TechnologyAlison Hayward - Massachusetts Institute of TechnologyAlexandra Scheiflinger - Beth Israel Deaconess Medical CenterKellie L Bodeker - University of IowaRitesh Kumar - Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, 08903, USAScott K Shaw - Department of Chemistry, The University of Iowa, Iowa City, IA, 52242, USASalma K Jabbour - Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, 08903, USAVitor A Lira - University of IowaMichael D Henry - University of IowaMichael S Tift - University of North Carolina WilmingtonLeo E Otterbein - Beth Israel Deaconess Medical CenterGiovanni Traverso - Massachusetts Institute of TechnologyJames D Byrne - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Advanced science, Vol.11(9), 2308346
- DOI
- 10.1002/advs.202308346
- PMID
- 38084435
- PMCID
- PMC10916612
- NLM abbreviation
- Adv Sci (Weinh)
- eISSN
- 2198-3844
- Publisher
- Wiley
- Grant note
- K08CA275908 / NCI NIH HHS NCI K08 CA276908 / NCI NIH HHS
- Language
- English
- Electronic publication date
- 12/12/2023
- Date published
- 03/06/2024
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Pathology; Radiation Oncology; Chemistry; Dental Research; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984530263102771
Metrics
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