The diagnostic significance of CDH17-positive circulating tumor cells in patients with colorectal cancer

Pei, Xiao M.; Wong, Heong Ting; Ng, Simon Siu Man; Leung, Wing Wa; Wong, Ying; Tsang, Hin Fung; Chan, Amanda; Wong, Yin Kwan; Yu, Allen Chi Shing; Yim, Aldrin Kay Yuen; Cho, William C.; Chan, John; Wong, Kwong Fai; Luk, John M.; Tai, Wei; Wong, Sze Chuen Cesar

doi:10.1080/14737159.2023.2176223

Cited by 4 publications

(5 citation statements)

References 73 publications

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“…CDH17 expression has been demonstrated in CRC human samples and can be used along with other markers, such as mucin 2 (MUC2) and cyclooxygenase-2 (COX-2), to predict disease progression and prognosis in CRC patients [ 18 , 21 ]. To further confirm the expression of CDH17 in CRC, the RNA expression of CDH17 in colon adenocarcinoma (COAD) tissues was examined using data from The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases.…”

Section: Resultsmentioning

confidence: 99%

“…It has uncovered that CDH17 is an oncogene for CRC development and could be used as a biomarker for prediction of CRC prognosis and metastasis [ 20 ]. Despite the high expression of CDH17 in CRC [ 21 ], and its maintenance in metastatic CRC tissues [ 14 ], targeting CDH17 for imaging-guided surgery in CRC remains unexplored.…”

Section: Introductionmentioning

confidence: 99%

“…We found that E8-Nbs can be used to efficiently visualize gastric tumors in vivo and deliver the immunotoxin PE38 (truncated Pseudomonas exotoxin A) in tumors, resulting in an outstanding tumor inhibitory effect [ 13 ]. Given that CDH17 is highly expressed in CRC with nearly 100% positivity, and its expression is correlated to poor prognosis [ 20 , 21 ]. We wonder whether E8 Nb conjugated with a NIR-II fluorescent agent could efficiently image CRC tumors and mediate imaging-guided surgical resection in murine CRC models.…”

Section: Introductionmentioning

confidence: 99%

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Cadherin 17 Nanobody-Mediated Near-Infrared-II Fluorescence Imaging-Guided Surgery and Immunotoxin Delivery for Colorectal Cancer

Ding,

Zhou,

Shi

et al. 2024

Biomater Res

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Surgery and targeted therapy are of equal importance for colorectal cancer (CRC) treatment. However, complete CRC tumor resection remains challenging, and new targeted agents are also needed for efficient CRC treatment. Cadherin 17 (CDH17) is a membrane protein that is highly expressed in CRC and, therefore, is an ideal target for imaging-guided surgery and therapeutics. This study utilizes CDH17 nanobody (E8-Nb) with the near-infrared (NIR) fluorescent dye IRDye800CW to construct a NIR-II fluorescent probe, E8-Nb-IR800CW, and a Pseudomonas exotoxin (PE)-based immunotoxin, E8-Nb-PE38, to evaluate their performance for CRC imaging, imaging-guided precise tumor excision, and antitumor effects. Our results show that E8-Nb-IR800CW efficiently recognizes CDH17 in CRC cells and tumor tissues, produces high-quality NIR-II images for CRC tumors, and enables precise tumor removal guided by NIR-II imaging. Additionally, fluorescent imaging confirms the targeting ability and specificity of the immunotoxin toward CDH17-positive tumors, providing the direct visible evidence for immunotoxin therapy. E8-Nb-PE38 immunotoxin markedly delays the growth of CRC through the induction of apoptosis and immunogenic cell death (ICD) in multiple CRC tumor models. Furthermore, E8-Nb-PE38 combined with 5-FU exerts synergistically antitumor effects and extends survival. This study highlights CDH17 as a promising target for CRC imaging, imaging-guided surgery, and drug delivery. Nanobodies targeting CDH17 hold great potential to construct NIR-II fluorescent probes for surgery navigation, and PE-based toxins fused with CDH17 nanobodies represent a novel therapeutic strategy for CRC treatment. Further investigation is warranted to validate these findings for potential clinical translation.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cadherin 17 Nanobody-Mediated Near-Infrared-II Fluorescence Imaging-Guided Surgery and Immunotoxin Delivery for Colorectal Cancer

Ding,

Zhou,

Shi

et al. 2024

Biomater Res

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“…Our previous study effectively demonstrated that the count of CTCs varies in relation to the tumor node metastasis (TNM) stage, as well as between pre-operative and post-operative phases. This result suggests their utility in tracking therapy responses [ 37 ] and offering prognostic and potentially predictive value [ 38 , 39 , 40 ] for patients with metastatic CRC. CTCs have been demonstrated in several studies to be associated with a poor prognosis and short overall survival in patients with CRC [ 41 ] and in the monitoring of metastatic process and disease progression [ 38 , 39 , 40 , 42 ].…”

Section: Blood-based Liquid Biopsy In Crcmentioning

confidence: 99%

“…This result suggests their utility in tracking therapy responses [ 37 ] and offering prognostic and potentially predictive value [ 38 , 39 , 40 ] for patients with metastatic CRC. CTCs have been demonstrated in several studies to be associated with a poor prognosis and short overall survival in patients with CRC [ 41 ] and in the monitoring of metastatic process and disease progression [ 38 , 39 , 40 , 42 ]. Furthermore, CTCs have the potential to provide valuable insights into the biology of CRC and the mechanisms of metastasis.…”

Section: Blood-based Liquid Biopsy In Crcmentioning

confidence: 99%

Exploring the Role of Circulating Cell-Free RNA in the Development of Colorectal Cancer

Kan

Pei

Yeung

et al. 2023

IJMS

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Circulating tumor RNA (ctRNA) has recently emerged as a novel and attractive liquid biomarker. CtRNA is capable of providing important information about the expression of a variety of target genes noninvasively, without the need for biopsies, through the use of circulating RNA sequencing. The overexpression of cancer-specific transcripts increases the tumor-derived RNA signal, which overcomes limitations due to low quantities of circulating tumor DNA (ctDNA). The purpose of this work is to present an up-to-date review of current knowledge regarding ctRNAs and their status as biomarkers to address the diagnosis, prognosis, prediction, and drug resistance of colorectal cancer. The final section of the article discusses the practical aspects involved in analyzing plasma ctRNA, including storage and isolation, detection technologies, and their limitations in clinical applications.

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Nanobody‐Engineered Biohybrid Bacteria Targeting Gastrointestinal Cancers Induce Robust STING‐Mediated Anti‐Tumor Immunity

Xu,

Ding,

Dong

et al. 2024

Advanced Science

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Bacteria can be utilized for cancer therapy owing to their preferential colonization at tumor sites. However, unmodified non‐pathogenic bacteria carry potential risks due to their non‐specific targeting effects, and their anti‐tumor activity is limited when used as monotherapy. In this study, a biohybrid‐engineered bacterial system comprising non‐pathogenic MG1655 bacteria modified with CDH17 nanobodies on their surface and conjugated with photosensitizer croconium (CR) molecules is developed. The resultant biohybrid bacteria can efficiently home to CDH17‐positive tumors, including gastric, pancreatic, and colorectal cancers, and significantly suppress tumor growth upon irradiation. More importantly, biohybrid bacteria‐mediated photothermal therapy (PTT) induced abundant macrophage infiltration in a syngeneic murine colorectal model. Further, that the STING pathway is activated in tumor macrophages by the released bacterial nucleic acid after PTT is revealed, leading to the production of type I interferons. The addition of CD47 nanobody but not PD‐1 antibody to the PTT regimen can eradicate the tumors and extend survival. This results indicate that bacteria endowed with tumor‐specific selectivity and coupled with photothermal payloads can serve as an innovative strategy for low‐immunogenicity cancers. This strategy can potentially reprogram the tumor microenvironment by inducing macrophage infiltration and enhancing the efficacy of immunotherapy targeting macrophages.

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The diagnostic significance of CDH17-positive circulating tumor cells in patients with colorectal cancer

Cited by 4 publications

References 73 publications

Cadherin 17 Nanobody-Mediated Near-Infrared-II Fluorescence Imaging-Guided Surgery and Immunotoxin Delivery for Colorectal Cancer

Cadherin 17 Nanobody-Mediated Near-Infrared-II Fluorescence Imaging-Guided Surgery and Immunotoxin Delivery for Colorectal Cancer

Exploring the Role of Circulating Cell-Free RNA in the Development of Colorectal Cancer

Nanobody‐Engineered Biohybrid Bacteria Targeting Gastrointestinal Cancers Induce Robust STING‐Mediated Anti‐Tumor Immunity

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