Modeling Colorectal Cancer Progression Reveals Niche-Dependent Clonal Selection

Vaquero-Siguero, Nuria; Schleußner, Nikolai; Volk, Julia; Mastel, Manuel; Meier, Jasmin; Jackstadt, René

doi:10.3390/cancers14174260

Cited by 7 publications

(2 citation statements)

References 63 publications

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“…174 Similarly, inhibition of ROCK2 activity increases the invasiveness of colorectal adenocarcinoma organoids. 175 Clonal selection and metastatic capacity exhibit ecotype dependence (Figure 4d), 176,177 but this stem cell niche factor dependence is progressively lost with cancer progression. 178…”

Section: Cd44 Interactions Between Tumor Cells and Subsequent Cd44-pak2mentioning

confidence: 99%

Flourishing tumor organoids: History, emerging technology, and application

Yang

et al. 2023

Bioengineering & Transla Med

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Malignant tumors are one of the leading causes of death which impose an increasingly heavy burden on all countries. Therefore, the establishment of research models that closely resemble original tumor characteristics is crucial to further understanding the mechanisms of malignant tumor development, developing safer and more effective drugs, and formulating personalized treatment plans. Recently, organoids have been widely used in tumor research owing to their advantages including preserving the structure, heterogeneity, and cellular functions of the original tumor, together with the ease of manipulation. This review describes the history and characteristics of tumor organoids and the synergistic combination of three‐dimensional (3D) culture approaches for tumor organoids with emerging technologies, including tissue‐engineered cell scaffolds, microfluidic devices, 3D bioprinting, rotating wall vessels, and clustered regularly interspaced short palindromic repeats‐CRISPR‐associated protein 9 (CRISPR‐Cas9). Additionally, the progress in research and the applications in basic and clinical research of tumor organoid models are summarized. This includes studies of the mechanism of tumor development, drug development and screening, precision medicine, immunotherapy, and simulation of the tumor microenvironment. Finally, the existing shortcomings of tumor organoids and possible future directions are discussed.

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Section: Cd44 Interactions Between Tumor Cells and Subsequent Cd44-pak2mentioning

confidence: 99%

Flourishing tumor organoids: History, emerging technology, and application

Yang

et al. 2023

Bioengineering & Transla Med

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“…3C), despite the lower metastatic potential of KPN intracolonic transplants compared with the autochthonous and the intra-splenic transplantation models 31 . Given the lower incidence of metastasis, we performed a further intracolonic transplantation using metastatic villin-creERT2 Apc / Kras G12D/+ Trp53 / Tgfbr1 / (AKPT)-derived organoids, which also model CMS4 32 . Once again, in this model, AZD7507 treatment had no impact on tumorigenesis or metastasis (Fig.…”

Section: Targeting Macrophages In Cms4 Carcinoma Modelsmentioning

confidence: 99%

Macrophage reprogramming—rather than depletion—is efficacious in a specific subset of colorectal tumor models

Mohamed,

Amirkhah,

Lavaud

et al. 2023

Preprint

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Despite the abundance of macrophages in colorectal cancer (CRC), macrophage-targeted therapy has not demonstrated significant clinical benefit. Here, we show that macrophage populations differ across the consensus molecular subtypes (CMS) of CRC and report the first preclinical study of macrophage targeting using mouse models stratified by CMS class. Whereas pan-macrophage ablation, using a CSF1R-inhibitor, lacked efficacy across CMS classes, genetic deletion of inflammatory chemokine receptors (iCCRs) reprogrammed macrophages towards an anti-tumorigenic phenotype, curtailing tumorigenesis in models of CMS1 CRC. We identify an iCCR-independent anti-tumorigenic antigen-presenting macrophage population necessary for therapeutic efficacy. We further show that individual targeting of the CCR1, CCR2, and CCR5 receptors on CRC macrophages lacks benefit, whereas their combined targeting holds promise. We propose that selective targeting of immunosuppressive macrophage populations, whilst sparing antigen-presenting subsets, should be considered when trialling macrophage-targeted therapies.

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