An immunocompetent rectal cancer model to study radiation therapy

Kim, Jin K.; Wu, Chao; Latto, Michael Del; Gao, Yajing; Choi, Seo‐Hyun; Kierstead, Maria; Sauvé, Charles-Etienne Gabriel; Fırat, Canan; Perez, Almudena Chaves; Sillanpaa, Jussi; Chen, Chin-Tung; Lawrence, Kayla E.; Paty, Philip B.; Barriga, Francisco M.; Wilkinson, John E.; Shia, Jinru; Sawyers, Charles L.; Lowe, Scott W.; García-Aguilar, Julio; Romesser, Paul B.; Smith, J. Joshua

doi:10.1016/j.crmeth.2022.100353

Cited by 2 publications

(2 citation statements)

References 45 publications

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“…[ 50 ] In these models, tumor establishment can be achieved via a colonoscopic submucosal injection of murine CRC-derived organoids into the rectal submucosa, [ 53 – 55 ] while there is also a role for carcinogen induction [ 56 ] and mechanical disruption. [ 57 ] Orthotopic models have reported high take rates and bestow clinical relevance on the preclinical platform in terms of tumorigenesis, local invasion, and metastatic routes, with the added benefit of allowing the tumor microenvironment to be studied in situ. [ 54 ] As a result of these characteristics, the orthotopic model's translational value increases, thus helping in the transition of radioimmunotherapy combinations for RC into clinical trials.…”

Section: Discussionmentioning

confidence: 99%

A Review of Scheduling Strategies for Radiotherapy and Immune Checkpoint Inhibition in Locally Advanced Rectal Cancer

Melissourgou-Syka,

Gillespie,

O'Cathail

et al. 2023

Journal of Immunotherapy and Precision Oncology

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Colorectal cancer (CRC) is the third most common malignancy across the globe and, despite advances in treatment strategies, survival rates remain low. Rectal cancer (RC) accounts for most of these cases, and traditional management strategies for advanced disease include total neoadjuvant therapy (TNT) with chemoradiotherapy followed by curative surgery. Unfortunately, approximately 10–15% of patients have no response to treatment or have recurrence at a short interval following radiotherapy. The introduction of immunotherapy in the form of immune checkpoint blockade (ICB) in metastatic colorectal cancer has improved clinical outcomes, yet most patients with RC present with microsatellite stable disease, which lacks the immune-rich microenvironment where ICB is most effective. There is evidence that combining radiotherapy with ICB can unlock the mechanisms that drive resistance in patients; however, the sequencing of these therapies is still debated. This review offers a comprehensive overview of clinical trials and preclinical models that use radiotherapy–immunotherapy combinations in RC in an attempt to extrapolate the ideal sequencing of the two treatment modalities. The results highlight the dearth of evidence to answer the question of whether ICB should be given before, during, or after radiotherapy, yet it is suggested that improving the relevance of our preclinical models will provide a platform with higher translational value and will lead to appropriate clinical trial designs.

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Section: Discussionmentioning

confidence: 99%

A Review of Scheduling Strategies for Radiotherapy and Immune Checkpoint Inhibition in Locally Advanced Rectal Cancer

Melissourgou-Syka,

Gillespie,

O'Cathail

et al. 2023

Journal of Immunotherapy and Precision Oncology

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“…Mice are frequently injected with conventional cell lines, which lack genetic and environmental heterogeneity, and typically exhibit only minimal tumor growth ( Olson et al., 2018 ; Arina et al., 2020 ). More recently, organoid mouse models of CRC have been established for testing radiotherapy ( Kim et al., 2022 ; Nicolas et al., 2022b ; Nicolas et al., 2022a ). However, these models have yet to be utilized for immunotherapy testing and microbiome research.…”

Section: Combined Radio- and Immunotherapy Treatmentmentioning

confidence: 99%

Dissecting the role of the gut microbiome and fecal microbiota transplantation in radio- and immunotherapy treatment of colorectal cancer

Van Dingenen,

Segers,

Wouters

et al. 2023

Front. Cell. Infect. Microbiol.

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Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and poses a major burden on the human health worldwide. At the moment, treatment of CRC consists of surgery in combination with (neo)adjuvant chemotherapy and/or radiotherapy. More recently, immune checkpoint blockers (ICBs) have also been approved for CRC treatment. In addition, recent studies have shown that radiotherapy and ICBs act synergistically, with radiotherapy stimulating the immune system that is activated by ICBs. However, both treatments are also associated with severe toxicity and efficacy issues, which can lead to temporary or permanent discontinuation of these treatment programs. There's growing evidence pointing to the gut microbiome playing a role in these issues. Some microorganisms seem to contribute to radiotherapy-associated toxicity and hinder ICB efficacy, while others seem to reduce radiotherapy-associated toxicity or enhance ICB efficacy. Consequently, fecal microbiota transplantation (FMT) has been applied to reduce radio- and immunotherapy-related toxicity and enhance their efficacies. Here, we have reviewed the currently available preclinical and clinical data in CRC treatment, with a focus on how the gut microbiome influences radio- and immunotherapy toxicity and efficacy and if these treatments could benefit from FMT.

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An immunocompetent rectal cancer model to study radiation therapy

Cited by 2 publications

References 45 publications

A Review of Scheduling Strategies for Radiotherapy and Immune Checkpoint Inhibition in Locally Advanced Rectal Cancer

A Review of Scheduling Strategies for Radiotherapy and Immune Checkpoint Inhibition in Locally Advanced Rectal Cancer

Dissecting the role of the gut microbiome and fecal microbiota transplantation in radio- and immunotherapy treatment of colorectal cancer

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