Engineered bacterial therapeutics for detecting and treating CRC

Nicole Siguenza¹, Arianna Brevi², Joanna T Zhang³, Arman Pabani⁴, Abhinav Bhushan⁴, Moumita Das⁵, Yousong Ding⁶, Jeff Hasty⁷, Pradipta Ghosh⁸, Amir Zarrinpar⁹

Affiliations

¹ Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA; Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
² Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
³ Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
⁴ Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA.
⁵ School of Physics and Astronomy, Rochester Institute of Technology, Rochester, NY, USA.
⁶ Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery and Development, University of Florida, Gainesville, FL, USA.
⁷ Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA; Synthetic Biology Institute, University of California, San Diego, La Jolla, CA, USA; Molecular Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA; Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.
⁸ Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
⁹ Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA; Synthetic Biology Institute, University of California, San Diego, La Jolla, CA, USA; Jennifer Moreno Department of Veterans Affairs, La Jolla, CA, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA; Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA. Electronic address: azarrinpar@ucsd.edu.

PMID: 38693003
PMCID: PMC11392429
DOI: 10.1016/j.trecan.2024.04.001

Review

Engineered bacterial therapeutics for detecting and treating CRC

Nicole Siguenza et al. Trends Cancer. 2024 Jul.

. 2024 Jul;10(7):588-597.

doi: 10.1016/j.trecan.2024.04.001. Epub 2024 Apr 30.

Authors

Nicole Siguenza¹, Arianna Brevi², Joanna T Zhang³, Arman Pabani⁴, Abhinav Bhushan⁴, Moumita Das⁵, Yousong Ding⁶, Jeff Hasty⁷, Pradipta Ghosh⁸, Amir Zarrinpar⁹

Affiliations

¹ Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA; Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
² Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
³ Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
⁴ Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA.
⁵ School of Physics and Astronomy, Rochester Institute of Technology, Rochester, NY, USA.
⁶ Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery and Development, University of Florida, Gainesville, FL, USA.
⁷ Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA; Synthetic Biology Institute, University of California, San Diego, La Jolla, CA, USA; Molecular Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA; Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.
⁸ Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
⁹ Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA; Synthetic Biology Institute, University of California, San Diego, La Jolla, CA, USA; Jennifer Moreno Department of Veterans Affairs, La Jolla, CA, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA; Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA, USA. Electronic address: azarrinpar@ucsd.edu.

PMID: 38693003
PMCID: PMC11392429
DOI: 10.1016/j.trecan.2024.04.001

Abstract

Despite an overall decrease in occurrence, colorectal cancer (CRC) remains the third most common cause of cancer deaths in the USA. Detection of CRC is difficult in high-risk groups, including those with genetic predispositions, with disease traits, or from certain demographics. There is emerging interest in using engineered bacteria to identify early CRC development, monitor changes in the adenoma and CRC microenvironment, and prevent cancer progression. Novel genetic circuits for cancer therapeutics or functions to enhance existing treatment modalities have been tested and verified in vitro and in vivo. Inclusion of biocontainment measures would prepare strains to meet therapeutic standards. Thus, engineered bacteria present an opportunity for detection and treatment of CRC lesions in a highly sensitive and specific manner.

Keywords: detection; engraftment; live bacterial therapeutics; treatment.

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Conflict of interest statement

Declaration of interests A.Z. has a patent for PCT/US18/27998 pending and licensed to Endure Biotherapeutics. A.Z. holds equity in and is the acting Chief Medical Officer of Endure Biotherapeutics. J.H. is a co-founder of GenCirq Inc, which focuses on cancer therapeutics. He is on the Board of Directors and has equity in GenCirq. His spouse is employed part time for the book-keeping and to support employees with Human Resources. The remaining authors have no interests to declare.

Figures

**Figure 1.. Interactions between the tumor and its microbiota.**
(A) Colorectal cancer progression from healthy epithelium to carcinoma. (B) Decreased oxygen, lower pH, and the necrotic core of a tumor are all microenvironmental factors thought to promote colonization of the tumor by certain bacteria. (C) Potential bacterial drivers of carcinogenesis are thought to cause inflammation, decreases in pH and oxygen concentrations, and DNA damage. Abbreviation: *pks*+, polyketide synthase positive.

**Figure 2.. The synchronized lysis circuit (SLC) [39] relies on a sufficiently high density of bacteria leading to the accumulation of quorum sensing molecules, causing synchronized cell lysis.**
The inducible SLC (iSLC) includes an additional exogenous inducer molecule that can be applied, modulating the population density requirements for subsequent synchronized lysis.

See this image and copyright information in PMC

References

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Engineered bacterial therapeutics for detecting and treating CRC

Affiliations

Engineered bacterial therapeutics for detecting and treating CRC

Authors

Affiliations

Abstract

Conflict of interest statement

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References

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Grants and funding

LinkOut - more resources

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