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Animal models and therapeutic molecular targets of cancer: utility and limitations.

Cekanova M, Rathore K - Drug Des Devel Ther (2014)

Bottom Line: Rodent models have revolutionized our ability to study gene and protein functions in vivo and to better understand their molecular pathways and mechanisms.Companion animals with spontaneous neoplasms are still an underexploited tool for making rapid advances in human and veterinary cancer therapies by testing new drugs and delivery systems that have shown promise in vitro and in vivo in mouse models.Shorter overall lifespan and more rapid disease progression are factors contributing to the advantages of a companion animal model.

View Article: PubMed Central - PubMed

Affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN, USA.

ABSTRACT
Cancer is the term used to describe over 100 diseases that share several common hallmarks. Despite prevention, early detection, and novel therapies, cancer is still the second leading cause of death in the USA. Successful bench-to-bedside translation of basic scientific findings about cancer into therapeutic interventions for patients depends on the selection of appropriate animal experimental models. Cancer research uses animal and human cancer cell lines in vitro to study biochemical pathways in these cancer cells. In this review, we summarize the important animal models of cancer with focus on their advantages and limitations. Mouse cancer models are well known, and are frequently used for cancer research. Rodent models have revolutionized our ability to study gene and protein functions in vivo and to better understand their molecular pathways and mechanisms. Xenograft and chemically or genetically induced mouse cancers are the most commonly used rodent cancer models. Companion animals with spontaneous neoplasms are still an underexploited tool for making rapid advances in human and veterinary cancer therapies by testing new drugs and delivery systems that have shown promise in vitro and in vivo in mouse models. Companion animals have a relatively high incidence of cancers, with biological behavior, response to therapy, and response to cytotoxic agents similar to those in humans. Shorter overall lifespan and more rapid disease progression are factors contributing to the advantages of a companion animal model. In addition, the current focus is on discovering molecular targets for new therapeutic drugs to improve survival and quality of life in cancer patients.

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Phylogenic trees of genes for different species.Notes: Phylogenetic trees of several cancer-related genes. (A) p53, (B) c-Myc, (C) COX-2, and (D) c-KIT/CD117, show that dog and cat genes are more similar to human genes when compared with those of the mouse. Sequence homology was compared using the Basic Local Alignment Search Tool from the National Center for Biotechnology Information and the phylogenetic trees were constructed based on the COBALT Multiple Sequence Alignment Tool with “neighbor joining” as the tree construction method.Abbreviations:c-KIT/CD117, tyrosine-protein kinase Kit/cluster of differentiation 117; c-Myc, cellular myelocytomatosis oncogene; COX-2, cyclooxygenase-2; p53, tumor suppressor p53.
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f2-dddt-8-1911: Phylogenic trees of genes for different species.Notes: Phylogenetic trees of several cancer-related genes. (A) p53, (B) c-Myc, (C) COX-2, and (D) c-KIT/CD117, show that dog and cat genes are more similar to human genes when compared with those of the mouse. Sequence homology was compared using the Basic Local Alignment Search Tool from the National Center for Biotechnology Information and the phylogenetic trees were constructed based on the COBALT Multiple Sequence Alignment Tool with “neighbor joining” as the tree construction method.Abbreviations:c-KIT/CD117, tyrosine-protein kinase Kit/cluster of differentiation 117; c-Myc, cellular myelocytomatosis oncogene; COX-2, cyclooxygenase-2; p53, tumor suppressor p53.

Mentions: High coverage dog genome sequencing has enabled better understanding of the genetics of cancer and allows comparisons in canines and humans.52 Recent studies have shown stronger similarities between the canine and human genome as compared with the mouse genome.50 The same tumor oncogenes and suppressor genes contribute to development of cancer in humans and dogs.50 The sequence homology between human and dog cancer-associated proteins, eg, p53, Rb, MDM2, BRCA1, and BRCA2,53,54 is similar, as shown in Table 1. A phylogenetic tree of the various cancer-related genes, including p53, c-Myc, cyclooxygenase-2 (COX-2), and c-KIT, shows that the dog and cat genes are more similar to human genes than to mouse genes, as shown in Figure 2. There are similarities in the cytogenetic abnormalities in human and canine cancers like fusion of the Abl gene (Abelson tyrosine kinase) to a part of the BCR (breakpoint cluster region) gene, which results in constitutively active BCR-Abl tyrosine kinase in leukemia,55 or presence of c-KIT mutations in gastrointestinal tumors56 in humans and canines. Dogs can develop a wide range of cancers, the most common being lymphoma, hemangiosarcoma, osteosarcoma (OSA), mast cell tumors, melanoma, squamous cell carcinoma, mammary carcinoma, apocrine gland carcinoma (anal sac), transitional cell carcinoma, and soft tissue sarcoma.50,57 Several types of cancer that might be suitable models for human cancer, along with the estimated percentage of all new cancers in dogs and cats in the USA, are summarized in Table 2.


Animal models and therapeutic molecular targets of cancer: utility and limitations.

Cekanova M, Rathore K - Drug Des Devel Ther (2014)

Phylogenic trees of genes for different species.Notes: Phylogenetic trees of several cancer-related genes. (A) p53, (B) c-Myc, (C) COX-2, and (D) c-KIT/CD117, show that dog and cat genes are more similar to human genes when compared with those of the mouse. Sequence homology was compared using the Basic Local Alignment Search Tool from the National Center for Biotechnology Information and the phylogenetic trees were constructed based on the COBALT Multiple Sequence Alignment Tool with “neighbor joining” as the tree construction method.Abbreviations:c-KIT/CD117, tyrosine-protein kinase Kit/cluster of differentiation 117; c-Myc, cellular myelocytomatosis oncogene; COX-2, cyclooxygenase-2; p53, tumor suppressor p53.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4206199&req=5

f2-dddt-8-1911: Phylogenic trees of genes for different species.Notes: Phylogenetic trees of several cancer-related genes. (A) p53, (B) c-Myc, (C) COX-2, and (D) c-KIT/CD117, show that dog and cat genes are more similar to human genes when compared with those of the mouse. Sequence homology was compared using the Basic Local Alignment Search Tool from the National Center for Biotechnology Information and the phylogenetic trees were constructed based on the COBALT Multiple Sequence Alignment Tool with “neighbor joining” as the tree construction method.Abbreviations:c-KIT/CD117, tyrosine-protein kinase Kit/cluster of differentiation 117; c-Myc, cellular myelocytomatosis oncogene; COX-2, cyclooxygenase-2; p53, tumor suppressor p53.
Mentions: High coverage dog genome sequencing has enabled better understanding of the genetics of cancer and allows comparisons in canines and humans.52 Recent studies have shown stronger similarities between the canine and human genome as compared with the mouse genome.50 The same tumor oncogenes and suppressor genes contribute to development of cancer in humans and dogs.50 The sequence homology between human and dog cancer-associated proteins, eg, p53, Rb, MDM2, BRCA1, and BRCA2,53,54 is similar, as shown in Table 1. A phylogenetic tree of the various cancer-related genes, including p53, c-Myc, cyclooxygenase-2 (COX-2), and c-KIT, shows that the dog and cat genes are more similar to human genes than to mouse genes, as shown in Figure 2. There are similarities in the cytogenetic abnormalities in human and canine cancers like fusion of the Abl gene (Abelson tyrosine kinase) to a part of the BCR (breakpoint cluster region) gene, which results in constitutively active BCR-Abl tyrosine kinase in leukemia,55 or presence of c-KIT mutations in gastrointestinal tumors56 in humans and canines. Dogs can develop a wide range of cancers, the most common being lymphoma, hemangiosarcoma, osteosarcoma (OSA), mast cell tumors, melanoma, squamous cell carcinoma, mammary carcinoma, apocrine gland carcinoma (anal sac), transitional cell carcinoma, and soft tissue sarcoma.50,57 Several types of cancer that might be suitable models for human cancer, along with the estimated percentage of all new cancers in dogs and cats in the USA, are summarized in Table 2.

Bottom Line: Rodent models have revolutionized our ability to study gene and protein functions in vivo and to better understand their molecular pathways and mechanisms.Companion animals with spontaneous neoplasms are still an underexploited tool for making rapid advances in human and veterinary cancer therapies by testing new drugs and delivery systems that have shown promise in vitro and in vivo in mouse models.Shorter overall lifespan and more rapid disease progression are factors contributing to the advantages of a companion animal model.

View Article: PubMed Central - PubMed

Affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN, USA.

ABSTRACT
Cancer is the term used to describe over 100 diseases that share several common hallmarks. Despite prevention, early detection, and novel therapies, cancer is still the second leading cause of death in the USA. Successful bench-to-bedside translation of basic scientific findings about cancer into therapeutic interventions for patients depends on the selection of appropriate animal experimental models. Cancer research uses animal and human cancer cell lines in vitro to study biochemical pathways in these cancer cells. In this review, we summarize the important animal models of cancer with focus on their advantages and limitations. Mouse cancer models are well known, and are frequently used for cancer research. Rodent models have revolutionized our ability to study gene and protein functions in vivo and to better understand their molecular pathways and mechanisms. Xenograft and chemically or genetically induced mouse cancers are the most commonly used rodent cancer models. Companion animals with spontaneous neoplasms are still an underexploited tool for making rapid advances in human and veterinary cancer therapies by testing new drugs and delivery systems that have shown promise in vitro and in vivo in mouse models. Companion animals have a relatively high incidence of cancers, with biological behavior, response to therapy, and response to cytotoxic agents similar to those in humans. Shorter overall lifespan and more rapid disease progression are factors contributing to the advantages of a companion animal model. In addition, the current focus is on discovering molecular targets for new therapeutic drugs to improve survival and quality of life in cancer patients.

Show MeSH
Related in: MedlinePlus