The Mouse Xenograft Model in Cancer Research

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Methods and Technologies Development".

Deadline for manuscript submissions: closed (15 July 2024) | Viewed by 4198

Special Issue Editor

Special Issue Information

Dear Colleagues,

Human-to-mouse cancer xenografts are commonly used in cancer research to study the effectiveness of new treatments and to gain a better understanding of cancer biology.

Xenografts can be made from a wide range of human cancers, including breast, prostate, lung and colon cancers. They can also be used to study the effects of different cancer therapies, such as chemotherapy, radiotherapy and immunotherapy, in a living organism.

The use of human-to-mouse cancer xenografts has become a valuable tool in cancer research because it allows researchers to study human cancer in a living organism in a way that is not possible with cell cultures or other in vitro models.

However, there are limitations to this technique. These models cannot recapitulate the complex interactions between tumour cells, stroma and the human immune system. In addition, the use of animal models raises ethical concerns, and there is an ongoing debate about the validity of using animal models to study human diseases.

In this context, this Special Issue aims to bring the attention of Cancers readers to advances, cutting-edge developments, expertise and know-how across all cancer types in regard to these valuable animal models of cancer. Thus, we cordially invite authors to submit original articles, reviews and opinions that highlight their potential as tools for basic, translational and even precision medicine. 

Dr. Konstantinos Dimas
Guest Editor

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Keywords

  • xenografts
  • patient-derived xenograft models
  • humanised mice
  • organoids
  • tumour biology
  • tumour microenvironment
  • immunotherapy
  • novel anticancer therapies
  • new biomarkers
  • precision medicine
  • gene therapy
  • epigenetics

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Published Papers (3 papers)

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Research

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12 pages, 4082 KiB  
Article
Simultaneous Autophagy and Androgen Receptor Inhibition in a Prostate Cancer Xenograft Model
by Souzan Salemi, Benedikt Kranzbühler, Valentin Baumgartner, Lara Breitenmoser, Aleksandar Kuzmanov, Fabienne Lehner and Daniel Eberli
Cancers 2024, 16(19), 3261; https://doi.org/10.3390/cancers16193261 - 25 Sep 2024
Viewed by 867
Abstract
Objective: Abi, when used in conjunction with prednisone, is an established treatment for advanced PCa. Our goal was to explore the level of autophagy induced by Abi treatment, both alone and in combination with the autophagy inhibitor Chl, in a castrated mouse xenograft [...] Read more.
Objective: Abi, when used in conjunction with prednisone, is an established treatment for advanced PCa. Our goal was to explore the level of autophagy induced by Abi treatment, both alone and in combination with the autophagy inhibitor Chl, in a castrated mouse xenograft model. Methods: LNCaP cells were injected into the left and right sides of the back of nude mice that had been previously castrated. Mice were divided into four groups and treated daily with intraperitoneal injections of vehicle (control), Abi (10 mg/kg), Abi (10 mg/kg) combined with Chl (10 mg/kg), or Chl (10 mg/kg), and were monitored for periods of 2 and 3 weeks. Results: A significant reduction in tumor weight was observed in mice treated with the combination therapy, as opposed to those receiving vehicle control, Abi, or Chl alone. Mice receiving Abi + Chl exhibited reduced expression of ATG5, Beclin 1, and LC3 punctuations, along with an increase in P62, as determined by immunofluorescence and WES analysis. AR expression decreased significantly in all treatment groups compared to the control. PSMA expression was highest in the vehicle and combined treatment groups after 3 weeks, with a significant reduction observed with Chl treatment. Conclusions: These findings demonstrate that Abi + Chl treatment lowers autophagy levels and suppresses tumors more effectively than Abi alone. Full article
(This article belongs to the Special Issue The Mouse Xenograft Model in Cancer Research)
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13 pages, 2932 KiB  
Article
A Humanized and Defucosylated Antibody against Podoplanin (humLpMab-23-f) Exerts Antitumor Activities in Human Lung Cancer and Glioblastoma Xenograft Models
by Hiroyuki Suzuki, Tomokazu Ohishi, Mika K. Kaneko and Yukinari Kato
Cancers 2023, 15(20), 5080; https://doi.org/10.3390/cancers15205080 - 20 Oct 2023
Cited by 4 | Viewed by 1566
Abstract
A cancer-specific anti-PDPN mAb, LpMab-23 (mouse IgG1, kappa), was established in our previous study. We herein produced a humanized IgG1 version (humLpMab-23) and defucosylated form (humLpMab-23-f) of an anti-PDPN mAb to increase ADCC activity. humLpMab-23 recognized PDPN-overexpressed Chinese hamster ovary [...] Read more.
A cancer-specific anti-PDPN mAb, LpMab-23 (mouse IgG1, kappa), was established in our previous study. We herein produced a humanized IgG1 version (humLpMab-23) and defucosylated form (humLpMab-23-f) of an anti-PDPN mAb to increase ADCC activity. humLpMab-23 recognized PDPN-overexpressed Chinese hamster ovary (CHO)-K1 (CHO/PDPN), PDPN-positive PC-10 (human lung squamous cell carcinoma), and LN319 (human glioblastoma) cells via flow cytometry. We then demonstrated that humLpMab-23-f induced ADCC and complement-dependent cytotoxicity against CHO/PDPN, PC-10, and LN319 cells in vitro and exerted high antitumor activity in mouse xenograft models, indicating that humLpMab-23-f could be useful as an antibody therapy against PDPN-positive lung squamous cell carcinomas and glioblastomas. Full article
(This article belongs to the Special Issue The Mouse Xenograft Model in Cancer Research)
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Review

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22 pages, 336 KiB  
Review
Murine Xenograft Models as Preclinical Tools in Endometrial Cancer Research
by Merve Yildiz, Andrea Romano and Sofia Xanthoulea
Cancers 2024, 16(23), 3994; https://doi.org/10.3390/cancers16233994 - 28 Nov 2024
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Abstract
Murine xenograft models are valuable and increasingly used preclinical tools in cancer research to understand disease pathogenesis and guide treatment options. The aim of this narrative review is to summarize the studies that employed mouse xenograft models, using cell lines, patient-derived tumors, or [...] Read more.
Murine xenograft models are valuable and increasingly used preclinical tools in cancer research to understand disease pathogenesis and guide treatment options. The aim of this narrative review is to summarize the studies that employed mouse xenograft models, using cell lines, patient-derived tumors, or organoids, in endometrial cancer (EC) research, detailing their methodology and main findings. We identified 27 articles reporting on heterotopic EC xenografts, including subcutaneous, subrenal capsule, intraperitoneal, and retro-orbital models, and 18 articles using orthotopic xenografts. Subcutaneous xenografts generated using either cell lines or patient tumors have been widely used; however, their low engraftment rates and the inability to recapitulate main clinical features such as metastases limit their translational value. Subrenal capsule models showed improved engraftment rates compared to subcutaneous models, but tumors exhibited slower and constrained tumor growth. Orthotopic models are technically more challenging to generate and monitor, but tumor growth occurs in a relevant microenvironment and EC ortho-xenografts exhibit high engraftment rates and metastases to clinically relevant sites. Cell line-based xenograft (CDX) models are attractive tools because they are convenient, easy to use, and amenable to genetic modifications, making them suitable for proof-of-concept approaches and large-scale studies. EC xenografts developed from patient tumors (PDTXs) are more labor/cost-intensive for their establishment but can capture the genetic and molecular heterogeneity within and across histologic subtypes and can inform personalized patient treatment. EC organoid-based xenograft (PDOX) models combine the advantages of both CDXs and PDTXs since they are more time- and cost-effective, faithfully maintain tumor characteristics and therapeutic responses, and can be genetically modified. Despite substantial progress in EC management, there are still several unmet needs. Efficient targeted treatments are currently indicated only for a small subgroup of patients, while women with recurrent or advanced-stage EC have very few therapeutic options and their prognosis remains unfavorable. Novel (targeted) drugs, combinational regimens and tools to predict the real drug response in patients are urgently needed. Xenograft models are expected to inform about disease mechanisms and to help identify novel therapeutic options and suitable target patients. Full article
(This article belongs to the Special Issue The Mouse Xenograft Model in Cancer Research)
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