Recent advances in the development of transplanted colorectal cancer mouse models

Yang, Yu-Shen; Liu, Chu-Yun; Wen, Dan; Gao, Dazhi; Lin, Shu; He, Hefan; Zhao, Xue-Feng

doi:10.1016/j.trsl.2022.07.003

Cited by 8 publications

(10 citation statements)

References 109 publications

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“…The subcutaneous PDX CRC model is commonly used as it is easy to operate, monitor, and resect with good tumor engraftment, while rarely generate metastases [ 66 ]. In contrast, the orthotopic PDX CRC model is more invasive, labor intensive, and difficult to monitor longitudinally; however, they are better models of metastases because they generate primary tumors and distant lung and liver metastases at similar rates observed in patients [ 64 , 66 , 67 , 68 , 69 ]. As such, orthotopic PDX CRC models are helpful to evaluate local invasive growth of primary tumors, study tumor–host interactions and therapeutic responses in their anatomical context, but preclinical therapeutic studies currently exclusively utilize subcutaneous PDX CRC models [ 70 ].…”

Section: Research Models Crcmentioning

confidence: 99%

“…Thus, we will elaborate more detail on these two models below. Technically complicated, expensive [53,64,65] RTR: Recapitulate therapeutic response; TME: Tumor microenvironment; TSI: Tumor-stroma interactions.…”

Section: Research Models Crcmentioning

confidence: 99%

“…sive, and difficult to monitor longitudinally; however, they are better models of metastases because they generate primary tumors and distant lung and liver metastases at similar rates observed in patients [64,[66][67][68][69]. As such, orthotopic PDX CRC models are helpful to evaluate local invasive growth of primary tumors, study tumor-host interactions and therapeutic responses in their anatomical context, but preclinical therapeutic studies currently exclusively utilize subcutaneous PDX CRC models [70].…”

Section: Pdx Crc Modelsmentioning

confidence: 99%

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Genetic Alterations of NF-κB and Its Regulators: A Rich Platform to Advance Colorectal Cancer Diagnosis and Treatment

Alipourgivi,

Motolani,

Qiu

et al. 2023

IJMS

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Colorectal cancer (CRC) is the third leading cause of cancer mortality in the United States, with an estimated 52,000 deaths in 2023. Though significant progress has been made in both diagnosis and treatment of CRC in recent years, genetic heterogeneity of CRC—the culprit for possible CRC relapse and drug resistance, is still an insurmountable challenge. Thus, developing more effective therapeutics to overcome this challenge in new CRC treatment strategies is imperative. Genetic and epigenetic changes are well recognized to be responsible for the stepwise development of CRC malignancy. In this review, we focus on detailed genetic alteration information about the nuclear factor (NF)-κB signaling, including both NF-κB family members, and their regulators, such as protein arginine methyltransferase 5 (PRMT5), and outer dynein arm docking complex subunit 2 (ODAD2, also named armadillo repeat-containing 4, ARMC4), etc., in CRC patients. Moreover, we provide deep insight into different CRC research models, with a particular focus on patient-derived xenografts (PDX) and organoid models, and their potential applications in CRC research. Genetic alterations on NF-κB signaling components are estimated to be more than 50% of the overall genetic changes identified in CRC patients collected by cBioportal for Cancer Genomics; thus, emphasizing its paramount importance in CRC progression. Consequently, various genetic alterations on NF-κB signaling may hold great promise for novel therapeutic development in CRC. Future endeavors may focus on utilizing CRC models (e.g., PDX or organoids, or isogenic human embryonic stem cell (hESC)-derived colonic cells, or human pluripotent stem cells (hPSC)-derived colonic organoids, etc.) to further uncover the underpinning mechanism of these genetic alterations in NF-κB signaling in CRC progression. Moreover, establishing platforms for drug discovery in dishes, and developing Biobanks, etc., may further pave the way for the development of innovative personalized medicine to treat CRC in the future.

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Section: Research Models Crcmentioning

confidence: 99%

Section: Research Models Crcmentioning

confidence: 99%

Section: Pdx Crc Modelsmentioning

confidence: 99%

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Genetic Alterations of NF-κB and Its Regulators: A Rich Platform to Advance Colorectal Cancer Diagnosis and Treatment

Alipourgivi,

Motolani,

Qiu

et al. 2023

IJMS

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“…Additionally, it has been demonstrated that PDX models preserve the heterogeneity of the underlying tumor in CRC [203][204][205][206]. To facilitate engraftment, monitoring and resecting the tumor s.c. implantation is the most common [13,156,207]; however, this model was created using tumor tissue cells that were extracted through enzymatic digestion in multiple investigations [208].…”

Section: Patient-derived Xenograft (Pdx) Modelsmentioning

confidence: 99%

“…The disease is influenced by various genetic, environmental, and lifestyle factors that can increase an individual's risk of developing the disease. The early diagnosis, detection and therapy of patients with CRC are vital (Table S1) [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Although extensive research has been performed in the last decade about CRC, important issues still need to be solved, such as early diagnosis of micro-metastases and chemotherapy resistance.…”

Section: Introductionmentioning

confidence: 99%

Experimental Murine Models for Colorectal Cancer Research

Neto

Rocha

Gaspar

et al. 2023

Cancers

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Colorectal cancer (CRC) is the third most prevalent malignancy worldwide and in both sexes. Numerous animal models for CRC have been established to study its biology, namely carcinogen-induced models (CIMs) and genetically engineered mouse models (GEMMs). CIMs are valuable for assessing colitis-related carcinogenesis and studying chemoprevention. On the other hand, CRC GEMMs have proven to be useful for evaluating the tumor microenvironment and systemic immune responses, which have contributed to the discovery of novel therapeutic approaches. Although metastatic disease can be induced by orthotopic injection of CRC cell lines, the resulting models are not representative of the full genetic diversity of the disease due to the limited number of cell lines suitable for this purpose. On the other hand, patient-derived xenografts (PDX) are the most reliable for preclinical drug development due to their ability to retain pathological and molecular characteristics. In this review, the authors discuss the various murine CRC models with a focus on their clinical relevance, benefits, and drawbacks. From all models discussed, murine CRC models will continue to be an important tool in advancing our understanding and treatment of this disease, but additional research is required to find a model that can correctly reflect the pathophysiology of CRC.

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