Submit to Genes Review for Genes Propose a Special Issue

Journal Browser

Animal Modeling in Cancer

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (31 August 2019) | Viewed by 67122

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special issue Animal Modeling in Cancer book cover image

Share This Special Issue

Special Issue Editor

Dr. Vladimir Korinek

E-Mail Website
Collection Editor

Department of Cell and Developmental Biology, Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic, Prague, Czech Republic
Interests: cell biology; genetics; gastrointestinal tract; intestinal epithelium; stem cells; colorectal cancer; Wnt signaling; TCF/LEF proteins; mouse models; gene targeting

Special Issue Information

Dear Colleagues,

The understanding of pathological mechanisms involved in human diseases and their possible treatment has been historically based on comparative analysis of diverse animal species that share similar genetic, physiological and behavioral composition. The ancient Greeks were the first to use animals as models for anatomy and physiology, and this was consequently adopted by other cultures and led to important discoveries in many biomedical disciplines.

Currently, there is a high interest in gene manipulation techniques as they have become a fundamental research tool to generate organisms that simulate diseases characteristics on which new research and treatments can be applied. Over the years, a large availability of methods to generate animal models has been developed including conditional alleles production, gene knock-ins, and RNA interference technologies that greatly contributed to our knowledge why and how diseases are initiated, developed, and, eventually, cured.

In the recent years, there have been many efforts to understand and fight cancer through new revolutionary personalized treatments and wider screenings that help diagnose and treat cancer effectively. A fundamental part of this effort is to develop suitable cancer animal models that simulate the different disease variants and their progression. Ranging from tumor-derived xenografts to genetically engineered models, a wide variety of systems are applied for this purpose and many technological breakthroughs are changing the way that cancer is studied and analysed.

In this Special Issue, we would like to collect a set of research articles and reviews that focus on the generation of cancer animal models that are used to understand the disease and contribute to design and test new drugs for cancer prevention or treatment in mice and in other vertebrate model organisms.

Dr. Vladimír Kořínek
Collection Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

cancer
mouse models
non-mouse models
gene editing
stem cells
solid tumors
hematologic malignancies

Published Papers (11 papers)

Download All Papers

Editorial

Jump to: Review

4 pages, 182 KiB

Open AccessEditorial

Special Issue: Animal Modeling in Cancer

by Vladimir Korinek

Genes 2020, 11(9), 1009; https://doi.org/10.3390/genes11091009 - 27 Aug 2020

Cited by 2 | Viewed by 1738

Abstract

Recent advances in high-throughput sequencing techniques have significantly accelerated the development of personalized diagnostic tools and cancer treatments. However, a comparative analysis of experimental animals that share similar genetic, physiological, and behavioral traits with humans remains the basis for understanding the pathological mechanisms associated with human diseases, including cancer. The generation and characterization of suitable animal models mimicking tumor growth and progression thus represents an important “component” of tumor biology research. The presented Special Issue contains ten review articles, which, based on data obtained from various animal models, summarize a number of aspects of the tumor formation process that include gastrointestinal neoplasia, breast cancer, hematological malignancies, melanoma, and brain tumors. This Special Issue nicely illustrates how the study of suitable living models uncovers not only the fundamental molecular and cellular bases of neoplastic growth, but might also indicate approaches to efficient cancer treatments. Full article

(This article belongs to the Special Issue Animal Modeling in Cancer)

Review

Jump to: Editorial

30 pages, 1172 KiB

Open AccessReview

Zebrafish Models of Cancer—New Insights on Modeling Human Cancer in a Non-Mammalian Vertebrate

by Martina Hason and Petr Bartůněk

Genes 2019, 10(11), 935; https://doi.org/10.3390/genes10110935 - 15 Nov 2019

Cited by 110 | Viewed by 13709

Abstract

Zebrafish (Danio rerio) is a valuable non-mammalian vertebrate model widely used to study development and disease, including more recently cancer. The evolutionary conservation of cancer-related programs between human and zebrafish is striking and allows extrapolation of research outcomes obtained in fish back to humans. Zebrafish has gained attention as a robust model for cancer research mainly because of its high fecundity, cost-effective maintenance, dynamic visualization of tumor growth in vivo, and the possibility of chemical screening in large numbers of animals at reasonable costs. Novel approaches in modeling tumor growth, such as using transgene electroporation in adult zebrafish, could improve our knowledge about the spatial and temporal control of cancer formation and progression in vivo. Looking at genetic as well as epigenetic alterations could be important to explain the pathogenesis of a disease as complex as cancer. In this review, we highlight classic genetic and transplantation models of cancer in zebrafish as well as provide new insights on advances in cancer modeling. Recent progress in zebrafish xenotransplantation studies and drug screening has shown that zebrafish is a reliable model to study human cancer and could be suitable for evaluating patient-derived xenograft cell invasiveness. Rapid, large-scale evaluation of in vivo drug responses and kinetics in zebrafish could undoubtedly lead to new applications in personalized medicine and combination therapy. For all of the above-mentioned reasons, zebrafish is approaching a future of being a pre-clinical cancer model, alongside the mouse. However, the mouse will continue to be valuable in the last steps of pre-clinical drug screening, mostly because of the highly conserved mammalian genome and biological processes. Full article

(This article belongs to the Special Issue Animal Modeling in Cancer)

► Show Figures

Figure 1

15 pages, 589 KiB

Open AccessReview

Cdx2 Animal Models Reveal Developmental Origins of Cancers

by Kallayanee Chawengsaksophak

Genes 2019, 10(11), 928; https://doi.org/10.3390/genes10110928 - 14 Nov 2019

Cited by 11 | Viewed by 3282

Abstract

The Cdx2 homeobox gene is important in assigning positional identity during the finely orchestrated process of embryogenesis. In adults, regenerative responses to tissues damage can require a replay of these same developmental pathways. Errors in reassigning positional identity during regeneration can cause metaplasias—normal tissue arising in an abnormal location—and this in turn, is a well-recognized cancer risk factor. In animal models, a gain of Cdx2 function can elicit a posterior shift in tissue identity, modeling intestinal-type metaplasias of the esophagus (Barrett’s esophagus) and stomach. Conversely, loss of Cdx2 function can elicit an anterior shift in tissue identity, inducing serrated-type lesions expressing gastric markers in the colon. These metaplasias are major risk factors for the later development of esophageal, stomach and colon cancer. Leukemia, another cancer in which Cdx2 is ectopically expressed, may have mechanistic parallels with epithelial cancers in terms of stress-induced reprogramming. This review will address how animal models have refined our understanding of the role of Cdx2 in these common human cancers. Full article

(This article belongs to the Special Issue Animal Modeling in Cancer)

► Show Figures

Figure 1

34 pages, 6137 KiB

Open AccessReview

Melanoma-Bearing Libechov Minipig (MeLiM): The Unique Swine Model of Hereditary Metastatic Melanoma

by Vratislav Horak, Anna Palanova, Jana Cizkova, Veronika Miltrova, Petr Vodicka and Helena Kupcova Skalnikova

Genes 2019, 10(11), 915; https://doi.org/10.3390/genes10110915 - 09 Nov 2019

Cited by 19 | Viewed by 6129

Abstract

National cancer databases document that melanoma is the most aggressive and deadly cutaneous malignancy with worldwide increasing incidence in the Caucasian population. Around 10% of melanomas occur in families. Several germline mutations were identified that might help to indicate individuals at risk for preventive interventions and early disease detection. More than 50% of sporadic melanomas carry mutations in Ras/Raf/mitogen-activated protein kinase (MAPK/MEK) pathway, which may represent aims of novel targeted therapies. Despite advances in targeted therapies and immunotherapies, the outcomes in metastatic tumor are still unsatisfactory. Here, we review animal models that help our understanding of melanoma development and treatment, including non-vertebrate, mouse, swine, and other mammal models, with an emphasis on those with spontaneously developing melanoma. Special attention is paid to the melanoma-bearing Libechov minipig (MeLiM). This original swine model of hereditary metastatic melanoma enables studying biological processes underlying melanoma progression, as well as spontaneous regression. Current histological, immunohistochemical, biochemical, genetic, hematological, immunological, and skin microbiome findings in the MeLiM model are summarized, together with development of new therapeutic approaches based on tumor devitalization. The ongoing study of molecular and immunological base of spontaneous regression in MeLiM model has potential to bring new knowledge of clinical importance. Full article

(This article belongs to the Special Issue Animal Modeling in Cancer)

► Show Figures

Figure 1

20 pages, 665 KiB

Open AccessReview

Gut Microbiota Influences Experimental Outcomes in Mouse Models of Colorectal Cancer

by Alyssa A. Leystra and Margie L. Clapper

Genes 2019, 10(11), 900; https://doi.org/10.3390/genes10110900 - 07 Nov 2019

Cited by 33 | Viewed by 5948

Abstract

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Mouse models are a valuable resource for use throughout the development and testing of new therapeutic strategies for CRC. Tumorigenesis and response to therapy in humans and mouse models alike are influenced by the microbial communities that colonize the gut. Differences in the composition of the gut microbiota can confound experimental findings and reduce the replicability and translatability of the resulting data. Despite this, the contribution of resident microbiota to preclinical tumor models is often underappreciated. This review does the following: (1) summarizes evidence that the gut microbiota influence CRC disease phenotypes; (2) outlines factors that can influence the composition of the gut microbiota; and (3) provides strategies that can be incorporated into the experimental design, to account for the influence of the microbiota on intestinal phenotypes in mouse models of CRC. Through careful experimental design and documentation, mouse models can continue to rapidly advance efforts to prevent and treat colon cancer. Full article

(This article belongs to the Special Issue Animal Modeling in Cancer)

► Show Figures

Figure 1

44 pages, 2871 KiB

Open AccessReview

Ubiquitin Ligases Involved in the Regulation of Wnt, TGF-β, and Notch Signaling Pathways and Their Roles in Mouse Development and Homeostasis

by Nikol Baloghova, Tomas Lidak and Lukas Cermak

Genes 2019, 10(10), 815; https://doi.org/10.3390/genes10100815 - 16 Oct 2019

Cited by 15 | Viewed by 7414

Abstract

The Wnt, TGF-β, and Notch signaling pathways are essential for the regulation of cellular polarity, differentiation, proliferation, and migration. Differential activation and mutual crosstalk of these pathways during animal development are crucial instructive forces in the initiation of the body axis and the development of organs and tissues. Due to the ability to initiate cell proliferation, these pathways are vulnerable to somatic mutations selectively producing cells, which ultimately slip through cellular and organismal checkpoints and develop into cancer. The architecture of the Wnt, TGF-β, and Notch signaling pathways is simple. The transmembrane receptor, activated by the extracellular stimulus, induces nuclear translocation of the transcription factor, which subsequently changes the expression of target genes. Nevertheless, these pathways are regulated by a myriad of factors involved in various feedback mechanisms or crosstalk. The most prominent group of regulators is the ubiquitin–proteasome system (UPS). To open the door to UPS-based therapeutic manipulations, a thorough understanding of these regulations at a molecular level and rigorous confirmation in vivo are required. In this quest, mouse models are exceptional and, thanks to the progress in genetic engineering, also an accessible tool. Here, we reviewed the current understanding of how the UPS regulates the Wnt, TGF-β, and Notch pathways and we summarized the knowledge gained from related mouse models. Full article

(This article belongs to the Special Issue Animal Modeling in Cancer)

► Show Figures

Figure 1

13 pages, 249 KiB

Open AccessReview

Experimental Modeling of Myeloproliferative Neoplasms

by Lucie Lanikova, Olga Babosova and Josef T. Prchal

Genes 2019, 10(10), 813; https://doi.org/10.3390/genes10100813 - 15 Oct 2019

Cited by 12 | Viewed by 4119

Abstract

Myeloproliferative neoplasms (MPN) are genetically very complex and heterogeneous diseases in which the acquisition of a somatic driver mutation triggers three main myeloid cytokine receptors, and phenotypically expresses as polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). The course of the diseases may be influenced by germline predispositions, modifying mutations, their order of acquisition and environmental factors such as aging and inflammation. Deciphering these contributory elements, their mutual interrelationships, and their contribution to MPN pathogenesis brings important insights into the diseases. Animal models (mainly mouse and zebrafish) have already significantly contributed to understanding the role of several acquired and germline mutations in MPN oncogenic signaling. Novel technologies such as induced pluripotent stem cells (iPSCs) and precise genome editing (using CRISPR/Cas9) contribute to the emerging understanding of MPN pathogenesis and clonal architecture, and form a convenient platform for evaluating drug efficacy. In this overview, the genetic landscape of MPN is briefly described, with an attempt to cover the main discoveries of the last 15 years. Mouse and zebrafish models of the driver mutations are discussed and followed by a review of recent progress in modeling MPN with patient-derived iPSCs and CRISPR/Cas9 gene editing. Full article

(This article belongs to the Special Issue Animal Modeling in Cancer)

33 pages, 2012 KiB

Open AccessReview

Human Colorectal Cancer from the Perspective of Mouse Models

by Monika Stastna, Lucie Janeckova, Dusan Hrckulak, Vitezslav Kriz and Vladimir Korinek

Genes 2019, 10(10), 788; https://doi.org/10.3390/genes10100788 - 11 Oct 2019

Cited by 25 | Viewed by 6746

Abstract

Colorectal cancer (CRC) is a heterogeneous disease that includes both hereditary and sporadic types of tumors. Tumor initiation and growth is driven by mutational or epigenetic changes that alter the function or expression of multiple genes. The genes predominantly encode components of various intracellular signaling cascades. In this review, we present mouse intestinal cancer models that include alterations in the Wnt, Hippo, p53, epidermal growth factor (EGF), and transforming growth factor β (TGFβ) pathways; models of impaired DNA mismatch repair and chemically induced tumorigenesis are included. Based on their molecular biology characteristics and mutational and epigenetic status, human colorectal carcinomas were divided into four so-called consensus molecular subtype (CMS) groups. It was shown subsequently that the CMS classification system could be applied to various cell lines derived from intestinal tumors and tumor-derived organoids. Although the CMS system facilitates characterization of human CRC, individual mouse models were not assigned to some of the CMS groups. Thus, we also indicate the possible assignment of described animal models to the CMS group. This might be helpful for selection of a suitable mouse strain to study a particular type of CRC. Full article

(This article belongs to the Special Issue Animal Modeling in Cancer)

► Show Figures

Figure 1

18 pages, 3862 KiB

Open AccessReview

Effects of Radiation Therapy on Neural Stem Cells

by Anna Michaelidesová, Jana Konířová, Petr Bartůněk and Martina Zíková

Genes 2019, 10(9), 640; https://doi.org/10.3390/genes10090640 - 24 Aug 2019

Cited by 26 | Viewed by 7416

Abstract

Brain and nervous system cancers in children represent the second most common neoplasia after leukemia. Radiotherapy plays a significant role in cancer treatment; however, the use of such therapy is not without devastating side effects. The impact of radiation-induced damage to the brain is multifactorial, but the damage to neural stem cell populations seems to play a key role. The brain contains pools of regenerative neural stem cells that reside in specialized neurogenic niches and can generate new neurons. In this review, we describe the advances in radiotherapy techniques that protect neural stem cell compartments, and subsequently limit and prevent the occurrence and development of side effects. We also summarize the current knowledge about neural stem cells and the molecular mechanisms underlying changes in neural stem cell niches after brain radiotherapy. Strategies used to minimize radiation-related damages, as well as new challenges in the treatment of brain tumors are also discussed. Full article

(This article belongs to the Special Issue Animal Modeling in Cancer)

► Show Figures

Figure 1

35 pages, 560 KiB

Open AccessReview

A Critical Review of Animal Models Used in Acute Myeloid Leukemia Pathophysiology

by Hala Skayneh, Batoul Jishi, Rita Hleihel, Maguy Hamieh, Nadine Darwiche, Ali Bazarbachi, Marwan El Sabban and Hiba El Hajj

Genes 2019, 10(8), 614; https://doi.org/10.3390/genes10080614 - 13 Aug 2019

Cited by 20 | Viewed by 6690

Abstract

Acute myeloid leukemia (AML) is one of the most frequent, complex, and heterogeneous hematological malignancies. AML prognosis largely depends on acquired cytogenetic, epigenetic, and molecular abnormalities. Despite the improvement in understanding the biology of AML, survival rates remain quite low. Animal models offer a valuable tool to recapitulate different AML subtypes, and to assess the potential role of novel and known mutations in disease progression. This review provides a comprehensive and critical overview of select available AML animal models. These include the non-mammalian Zebrafish and Drosophila models as well as the mammalian rodent systems, comprising rats and mice. The suitability of each animal model, its contribution to the advancement of knowledge in AML pathophysiology and treatment, as well as its advantages and limitations are discussed. Despite some limitations, animal models represent a powerful approach to assess toxicity, and permit the design of new therapeutic strategies. Full article

(This article belongs to the Special Issue Animal Modeling in Cancer)

14 pages, 288 KiB

Open AccessReview

Rodent Models Assessing Mammary Tumor Prevention by Soy or Soy Isoflavones

by Roger A. Moorehead

Genes 2019, 10(8), 566; https://doi.org/10.3390/genes10080566 - 26 Jul 2019

Cited by 7 | Viewed by 3025

Abstract

While epidemiological studies performed in Asian countries generally show that high levels of dietary soy are associated with reduced breast cancer risk, studies in Western countries have typically failed to show this correlation. In an attempt to model the preventative actions of soy on mammary tumor development, rodent models have been employed. Thirty-four studies were identified that evaluated the impact of soy products or purified soy isoflavones on mammary tumor initiation (studies evaluating established mammary tumors or mammary tumor cell lines were not included) and these studies were separated into mammary tumors induced by chemical carcinogens or transgenic expression of oncogenes based on the timing of soy administration. Regardless of when soy-based diets or purified isoflavones were administered, no consistent protective effects were observed in either carcinogen-induced or oncogene-induced mammary tumors. While some studies demonstrated that soy or purified isoflavones could reduce mammary tumor incidence, other studies showed either no effect or tumor promoting effects of soy products or isoflavones. Most importantly, only five studies found a decrease in mammary tumor incidence and six studies observed a decrease in tumor multiplicity, two relevant measures of the tumor preventative effects of soy or isoflavones. The variable outcomes of the studies examined were not completely surprising given that few studies employed the same experimental design. Future studies should be carefully designed to more accurately emulate soy consumption observed in Asian cultures including lifetime exposure to less refined soy products and potentially the incorporation of multigenerational feeding studies. Full article

(This article belongs to the Special Issue Animal Modeling in Cancer)

Journal Menu

Journal Browser

Animal Modeling in Cancer

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (11 papers)

Editorial

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI