Oral Carbon Monoxide Enhances Autophagy Modulation in Prostate, Pancreatic, and Lung Cancers
Name
Advanced Science - 2023 - Bi - Oral Carbon Monoxide Enhances Autophagy Modulation in Prostate Pancreatic and Lung Cancers.pdf
Description
Accepted version
Size
3.39 MB
Format
Adobe PDF
Checksum (MD5)
aa3ab56bd1137aa3b7f92fbd10af27fe
Author(s)
Bi, Jianling
Witt, Emily
McGovern, Megan K.
Cafi, Arielle B.
Rosenstock, Lauren L.
Pearson, Anna B.
Brown, Timothy J.
Karasic, Thomas B.
Absler, Lucas C.
Machkanti, Srija
Date Issued
December 12, 2023
Journal
Advanced Science
Publisher
Wiley
Citation
J. Bi, E. Witt, M. K. McGovern, A. B. Cafi, L. L. Rosenstock, A. B. Pearson, T. J. Brown, T. B. Karasic, L. C. Absler, S. Machkanti, H. Boyce, D. Gallo, S. L. Becker, K. Ishida, J. Jenkins, A. Hayward, A. Scheiflinger, K. L. Bodeker, R. Kumar, S. K. Shaw, S. K. Jabbour, V. A. Lira, M. D. Henry, M. S. Tift, L. E. Otterbein, G. Traverso, J. D. Byrne, Oral Carbon Monoxide Enhances Autophagy Modulation in Prostate, Pancreatic, and Lung Cancers. Adv. Sci. 2024, 11, 2308346.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Mechanical Engineering
Massachusetts Institute of Technology. Division of Comparative Medicine
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1002/advs.202308346
