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Review
. 2024 Jul;10(7):588-597.
doi: 10.1016/j.trecan.2024.04.001. Epub 2024 Apr 30.

Engineered bacterial therapeutics for detecting and treating CRC

Affiliations
Review

Engineered bacterial therapeutics for detecting and treating CRC

Nicole Siguenza et al. Trends Cancer. 2024 Jul.

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.
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.
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.

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