Special Issue "Comparative Pathogenesis of Cancers in Animals and Humans"

A special issue of Veterinary Sciences (ISSN 2306-7381).

Deadline for manuscript submissions: closed (31 May 2015).

Special Issue Editor

Jaime F. Modiano, VMD, PhD
Website
Guest Editor
College of Veterinary Medicine and Masonic Cancer Center, University of Minnesota, Saint Paul, MN 55108, USA
Interests: The research emphasis in Dr. Modiano’s laboratory is to understand how and why cancer happens and to translate basic research into clinical applications that improve the health and wellbeing of companion animals and humans

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Published Papers (19 papers)

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Editorial

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Open AccessEditorial
Comparative Pathogenesis of Cancers in Animals and Humans
Vet. Sci. 2016, 3(3), 24; https://doi.org/10.3390/vetsci3030024 - 13 Sep 2016
Cited by 1
Abstract
As Guest Editor of Veterinary Sciences, I am honored to introduce the special issue, “Comparative Pathogenesis of Cancers in Animals and Humans”.[...] Full article
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)

Review

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Open AccessReview
The Comparative Diagnostic Features of Canine and Human Lymphoma
Vet. Sci. 2016, 3(2), 11; https://doi.org/10.3390/vetsci3020011 - 09 Jun 2016
Cited by 24
Abstract
The non-Hodgkin lymphomas (NHLs) are a heterogeneous family of lymphoid malignancies that are among the most common neoplasms of both dogs and humans. Owing to shared molecular, signaling, incidence, and pathologic features, there is a strong framework supporting the utilization of canine lymphoma [...] Read more.
The non-Hodgkin lymphomas (NHLs) are a heterogeneous family of lymphoid malignancies that are among the most common neoplasms of both dogs and humans. Owing to shared molecular, signaling, incidence, and pathologic features, there is a strong framework supporting the utilization of canine lymphoma as a comparative, large animal model of human NHL. In alignment with the biologic similarities, the current approach towards the diagnosis and classification of canine lymphoma is based upon the human World Health Organization guidelines. While this approach has contributed to an increasing appreciation of the potential biological scope of canine lymphoma, it has also become apparent that the most appropriate diagnostic philosophy must be multimodal, namely by requiring knowledge of microscopic, immunophenotypic, and clinical features before establishing a final disease diagnosis. This review seeks to illustrate the comparative similarities and differences in the diagnosis of canine lymphoma through the presentation of the microscopic and immunophenotypic features of its most common forms. Full article
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)
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Open AccessReview
Comparative Aspects of Canine Melanoma
Vet. Sci. 2016, 3(1), 7; https://doi.org/10.3390/vetsci3010007 - 19 Feb 2016
Cited by 24
Abstract
Melanomas are malignant neoplasms originating from melanocytes. They occur in most animal species, but the dog is considered the best animal model for the disease. Melanomas in dogs are most frequently found in the buccal cavity, but the skin, eyes, and digits are [...] Read more.
Melanomas are malignant neoplasms originating from melanocytes. They occur in most animal species, but the dog is considered the best animal model for the disease. Melanomas in dogs are most frequently found in the buccal cavity, but the skin, eyes, and digits are other common locations for these neoplasms. The aim of this review is to report etiological, epidemiological, pathological, and molecular aspects of melanomas in dogs. Furthermore, the particular biological behaviors of these tumors in the different body locations are shown. Insights into the therapeutic approaches are described. Surgery, chemotherapy, radiotherapy, immunotherapy, and the outcomes after these treatments are presented. New therapeutic perspectives are also depicted. All efforts are geared toward better characterization and control of malignant melanomas in dogs, for the benefit of these companion animals, and also in an attempt to benefit the treatment of human melanomas. Full article
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)
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Open AccessReview
Therapeutic Innovations: Tyrosine Kinase Inhibitors in Cancer
Vet. Sci. 2016, 3(1), 4; https://doi.org/10.3390/vetsci3010004 - 20 Jan 2016
Cited by 8
Abstract
Conventional cytotoxic chemotherapy involving DNA-interacting agents and indiscriminate cell death is no longer the future of cancer management. While chemotherapy is not likely to completely disappear from the armamentarium; the use of targeted therapies in combination with conventional treatment is becoming the standard [...] Read more.
Conventional cytotoxic chemotherapy involving DNA-interacting agents and indiscriminate cell death is no longer the future of cancer management. While chemotherapy is not likely to completely disappear from the armamentarium; the use of targeted therapies in combination with conventional treatment is becoming the standard of care in human medicine. Tyrosine kinases are pivotal points of functional cellular pathways and have been implicated in malignancy, inflammatory, and immune-mediated diseases. Pharmaceutical interventions targeting aberrant tyrosine kinase signaling has exploded and is the second most important area of drug development. The “Valley of Death” between drug discovery and approval threatens to blunt the enormous strides in cancer management seen thus far. Kinase inhibitors, as targeted small molecules, hold promise in the treatment and diagnosis of cancer. However, there are still many unanswered questions regarding the use of kinase inhibitors in the interpretation and management of cancer. Comparative oncology has the potential to address restrictions and limitations in the advancement in kinase inhibitor therapy. Full article
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)
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Open AccessReview
Understanding the Osteosarcoma Pathobiology: A Comparative Oncology Approach
Vet. Sci. 2016, 3(1), 3; https://doi.org/10.3390/vetsci3010003 - 18 Jan 2016
Cited by 14
Abstract
Osteosarcoma is an aggressive primary bone tumor in humans and is among the most common cancer afflicting dogs. Despite surgical advancements and intensification of chemo- and targeted therapies, the survival outcome for osteosarcoma patients is, as of yet, suboptimal. The presence of metastatic [...] Read more.
Osteosarcoma is an aggressive primary bone tumor in humans and is among the most common cancer afflicting dogs. Despite surgical advancements and intensification of chemo- and targeted therapies, the survival outcome for osteosarcoma patients is, as of yet, suboptimal. The presence of metastatic disease at diagnosis or its recurrence after initial therapy is a major factor for the poor outcomes. It is thought that most human and canine patients have at least microscopic metastatic lesions at diagnosis. Osteosarcoma in dogs occurs naturally with greater frequency and shares many biological and clinical similarities with osteosarcoma in humans. From a genetic perspective, osteosarcoma in both humans and dogs is characterized by complex karyotypes with highly variable structural and numerical chromosomal aberrations. Similar molecular abnormalities have been observed in human and canine osteosarcoma. For instance, loss of TP53 and RB regulated pathways are common. While there are several oncogenes that are commonly amplified in both humans and dogs, such as MYC and RAS, no commonly activated proto-oncogene has been identified that could form the basis for targeted therapies. It remains possible that recurrent aberrant gene expression changes due to gene amplification or epigenetic alterations could be uncovered and these could be used for developing new, targeted therapies. However, the remarkably high genomic complexity of osteosarcoma has precluded their definitive identification. Several advantageous murine models of osteosarcoma have been generated. These include spontaneous and genetically engineered mouse models, including a model based on forward genetics and transposon mutagenesis allowing new genes and genetic pathways to be implicated in osteosarcoma development. The proposition of this review is that careful comparative genomic studies between human, canine and mouse models of osteosarcoma may help identify commonly affected and targetable pathways for alternative therapies for osteosarcoma patients. Translational research may be found through a path that begins in mouse models, and then moves through canine patients, and then human patients. Full article
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)
Open AccessReview
Canine Histiocytic Malignancies—Challenges and Opportunities
Vet. Sci. 2016, 3(1), 2; https://doi.org/10.3390/vetsci3010002 - 04 Jan 2016
Cited by 3
Abstract
Canine histiocytic malignancies (HM) are aggressive tumors that occur with particularly high frequency in certain breeds including Bernese mountain dogs and flat-coated retrievers. Robust diagnosis of HM commonly utilizes immunohistochemical stains that are broadly ineffective on formalin-fixed tissues; thus the diagnosis is often [...] Read more.
Canine histiocytic malignancies (HM) are aggressive tumors that occur with particularly high frequency in certain breeds including Bernese mountain dogs and flat-coated retrievers. Robust diagnosis of HM commonly utilizes immunohistochemical stains that are broadly ineffective on formalin-fixed tissues; thus the diagnosis is often one of exclusion. Clinical outcomes are generally poor, with frequent metastasis and therapeutic failure lowering overall survival at time of diagnosis to an average of less than two months in the majority of published work. The limited understanding of the molecular mechanisms underlying HM has hindered the development of more effective diagnostic modalities and the identification of therapeutic targets. A potential avenue exists for advancing clinical management of canine cancers through extrapolation from a close counterpart in human medicine. Historically, HM have been compared to the rare and understudied subset of human cancers involving the dendritic lineage, such as dendritic cell sarcoma or Langerhans cell sarcoma. Recent data have now thrown into question the cellular origin of HM, suggesting that the disease may originate from the macrophage lineage. This review summarizes existing knowledge of HM from the clinical, histologic and molecular perspectives, and highlights avenues for future research that may aid the development of novel diagnostic and therapeutic approaches. In turn, a more advanced appreciation of the mechanisms underlying HM should clarify their cellular origin and identify appropriate opportunities for synergistic extrapolation between related canine and human cancers. Full article
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)
Open AccessReview
Canine Mammary Carcinomas: A Comparative Analysis of Altered Gene Expression
Vet. Sci. 2016, 3(1), 1; https://doi.org/10.3390/vetsci3010001 - 25 Dec 2015
Cited by 8
Abstract
Breast cancer represents the second most frequent neoplasm in humans and sexually intact female dogs after lung and skin cancers, respectively. Many similar features in human and dog cancers including, spontaneous development, clinical presentation, tumor heterogeneity, disease progression and response to conventional therapies [...] Read more.
Breast cancer represents the second most frequent neoplasm in humans and sexually intact female dogs after lung and skin cancers, respectively. Many similar features in human and dog cancers including, spontaneous development, clinical presentation, tumor heterogeneity, disease progression and response to conventional therapies have supported development of this comparative model as an alternative to mice. The highly conserved similarities between canine and human genomes are also key to this comparative analysis, especially when compared to the murine genome. Studies with canine mammary tumor (CMT) models have shown a strong genetic correlation with their human counterparts, particularly in terms of altered expression profiles of cell cycle regulatory genes, tumor suppressor and oncogenes and also a large group of non-coding RNAs or microRNAs (miRNAs). Because CMTs are considered predictive intermediate models for human breast cancer, similarities in genetic alterations and cancer predisposition between humans and dogs have raised further interest. Many cancer-associated genetic defects critical to mammary tumor development and oncogenic determinants of metastasis have been reported and appear to be similar in both species. Comparative analysis of deregulated gene sets or cancer signaling pathways has shown that a significant proportion of orthologous genes are comparably up- or down-regulated in both human and dog breast tumors. Particularly, a group of cell cycle regulators called cyclin-dependent kinase inhibitors (CKIs) acting as potent tumor suppressors are frequently defective in CMTs. Interestingly, comparative analysis of coding sequences has also shown that these genes are highly conserved in mammals in terms of their evolutionary divergence from a common ancestor. Moreover, co-deletion and/or homozygous loss of the INK4A/ARF/INK4B (CDKN2A/B) locus, encoding three members of the CKI tumor suppressor gene families (p16/INK4A, p14ARF and p15/INK4B), in many human and dog cancers including mammary carcinomas, suggested their important conserved genetic order and localization in orthologous chromosomal regions. miRNAs, as powerful post-transcriptional regulators of most of the cancer-associated genes, have not been well evaluated to date in animal cancer models. Comprehensive expression profiles of miRNAs in CMTs have revealed their altered regulation showing a strong correlation with those found in human breast cancers. These genetic correlations between human and dog mammary cancers will greatly advance our understanding of regulatory mechanisms involving many critical cancer-associated genes that promote neoplasia and contribute to the promising development of future therapeutics. Full article
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)
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Open AccessReview
Manipulation of Innate Immunity for Cancer Therapy in Dogs
Vet. Sci. 2015, 2(4), 423-439; https://doi.org/10.3390/vetsci2040423 - 01 Dec 2015
Cited by 10
Abstract
Over the last one to two decades, the field of cancer immunotherapy has rapidly progressed from early preclinical studies to a successful clinical reality and fourth major pillar of human cancer therapy. While current excitement in the field of immunotherapy is being driven [...] Read more.
Over the last one to two decades, the field of cancer immunotherapy has rapidly progressed from early preclinical studies to a successful clinical reality and fourth major pillar of human cancer therapy. While current excitement in the field of immunotherapy is being driven by several major breakthroughs including immune checkpoint inhibitors and adoptive cell therapies, these advances stem from a foundation of pivotal studies demonstrating the immune systems role in tumor control and eradication. The following will be a succinct review on veterinary cancer immunotherapy as it pertains to manipulation of the innate immune system to control tumor growth and metastasis. In addition, we will provide an update on recent progress in our understanding of the innate immune system in veterinary tumor immunology, and how these gains may lead to novel therapies for the treatment of cancer in companion animals. Full article
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)
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Open AccessReview
Pathobiology of Hemangiosarcoma in Dogs: Research Advances and Future Perspectives
Vet. Sci. 2015, 2(4), 388-405; https://doi.org/10.3390/vetsci2040388 - 06 Nov 2015
Cited by 24
Abstract
Hemangiosarcoma (HSA) is an aggressive and common cancer in dogs. While cutaneous masses are often treatable by tumor excision, visceral tumors are almost always incurable. Treatment advances for this disease have been limited due to a poor understanding of the overall tumor biology. [...] Read more.
Hemangiosarcoma (HSA) is an aggressive and common cancer in dogs. While cutaneous masses are often treatable by tumor excision, visceral tumors are almost always incurable. Treatment advances for this disease have been limited due to a poor understanding of the overall tumor biology. Based upon its histological appearance, HSA has been presumed to originate from transformed endothelial cells; however, accumulating data now suggest a pluripotent bone marrow progenitor as the cell of origin for this disease. More recently, the identification of a novel subclassification of HSAs has provided a foundation to further our understanding of the cellular characteristics of HSA tumor cells, along with those of the cells comprising the tumor microenvironment. These discoveries hold promise for the development of new approaches to improve treatments for canine HSA, as well as to establish the utility of this disease as a spontaneous model to understand the pathogenesis and develop new treatments for vascular tumors of humans. In this review, we will provide a brief historical perspective and pathobiology of canine HSA, along with a focus on the recent advances in the molecular and cellular understanding of these tumors. In addition, future directions that should continue to improve our understanding of HSA pathogenesis will be discussed. Full article
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)
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Open AccessReview
Progress in Adaptive Immunotherapy for Cancer in Companion Animals: Success on the Path to a Cure
Vet. Sci. 2015, 2(4), 363-387; https://doi.org/10.3390/vetsci2040363 - 19 Oct 2015
Cited by 15
Abstract
Harnessing the ability of the immune system to eradicate cancer has been a long-held goal of oncology. Work from the last two decades has finally brought immunotherapy into the forefront for cancer treatment, with demonstrable clinical success for aggressive tumors where other therapies [...] Read more.
Harnessing the ability of the immune system to eradicate cancer has been a long-held goal of oncology. Work from the last two decades has finally brought immunotherapy into the forefront for cancer treatment, with demonstrable clinical success for aggressive tumors where other therapies had failed. In this review, we will discuss a range of therapies that are in different stages of clinical or preclinical development for companion animals with cancer, and which share the common objective of eliciting adaptive, anti-tumor immune responses. Even though challenges remain, manipulating the immune system holds significant promise to create durable responses and improve outcomes in companion animals with cancer. Furthermore, what we learn from this process will inform and accelerate development of comparable therapies for human cancer patients. Full article
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)
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Open AccessReview
Beta Adrenergic Signaling: A Targetable Regulator of Angiosarcoma and Hemangiosarcoma
Vet. Sci. 2015, 2(3), 270-292; https://doi.org/10.3390/vetsci2030270 - 21 Sep 2015
Cited by 4
Abstract
Human angiosarcomas and canine hemangiosarcomas are highly aggressive cancers thought to arise from cells of vascular origin. The pathological features, morphological organization, and clinical behavior of canine hemangiosarcomas are virtually indistinct from those of human angiosarcomas. Overall survival with current standard-of-care approaches remains [...] Read more.
Human angiosarcomas and canine hemangiosarcomas are highly aggressive cancers thought to arise from cells of vascular origin. The pathological features, morphological organization, and clinical behavior of canine hemangiosarcomas are virtually indistinct from those of human angiosarcomas. Overall survival with current standard-of-care approaches remains dismal for both humans and dogs, and each is likely to succumb to their disease within a short duration. While angiosarcomas in humans are extremely rare, limiting their study and treatment options, canine hemangiosarcomas occur frequently. Therefore, studies of these sarcomas in dogs can be used to advance treatment approaches for both patient groups. Emerging data suggest that angiosarcomas and hemangiosarcomas utilize beta adrenergic signaling to drive their progression by regulating the tumor cell niche and fine-tuning cellular responses within the tumor microenvironment. These discoveries indicate that inhibition of beta adrenergic signaling could serve as an Achilles heel for these tumors and emphasize the need to design therapeutic strategies that target tumor cell and stromal cell constituents. In this review, we summarize recent discoveries and present new hypotheses regarding the roles of beta adrenergic signaling in angiosarcomas and hemangiosarcomas. Because the use of beta adrenergic receptor antagonists is well established in human and veterinary medicine, beta blockade could provide an immediate adjunct therapy for treatment along with a tangible opportunity to improve upon the outcomes of both humans and dogs with these diseases. Full article
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)
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Open AccessReview
Cytogenomics of Feline Cancers: Advances and Opportunities
Vet. Sci. 2015, 2(3), 246-258; https://doi.org/10.3390/vetsci2030246 - 31 Aug 2015
Cited by 7
Abstract
Relative to the dog, integration of the cat into the “One Health” concept has been more restricted, particularly in the field of molecular oncology. Beyond the continual need to enhance the sophistication of feline healthcare per se, the unique spectrum of naturally-occurring [...] Read more.
Relative to the dog, integration of the cat into the “One Health” concept has been more restricted, particularly in the field of molecular oncology. Beyond the continual need to enhance the sophistication of feline healthcare per se, the unique spectrum of naturally-occurring cancers in the cat offers tremendous opportunities for comparative and translational advances that may have mutual benefit for human and veterinary medicine. The study of feline cancers additionally may generate new insight into underexplored aspects of tumor biology that are less accessible in other species, such as the relationship between chronic inflammation and neoplasia, and the role of viruses in malignant transformation. Several factors that have hindered molecular studies of feline cancers have now been surmounted, with the most fundamental step forward coming from the development of a high-quality reference genome sequence assembly for the cat. This article reviews landmark studies that have led to our current appreciation of feline genome architecture, and outlines techniques used in cancer cytogenomics, from conventional karyotyping analysis through to the development of genomic microarrays and beyond. A summary of progress in the identification and characterization of chromosomal aberrations in feline cancers is provided using examples from studies of injection-site sarcomas, lymphomas and mammary tumors. Full article
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)
Open AccessReview
Comparative Aspects of BRAF Mutations in Canine Cancers
Vet. Sci. 2015, 2(3), 231-245; https://doi.org/10.3390/vetsci2030231 - 24 Aug 2015
Cited by 10
Abstract
Activating mutations of the BRAF gene lead to constitutive activation of the MAPK pathway. The characterization and discovery of BRAF mutations in a variety of human cancers has led to the development of specific inhibitors targeting the BRAF/MAPK pathway and dramatically changed clinical [...] Read more.
Activating mutations of the BRAF gene lead to constitutive activation of the MAPK pathway. The characterization and discovery of BRAF mutations in a variety of human cancers has led to the development of specific inhibitors targeting the BRAF/MAPK pathway and dramatically changed clinical outcomes in BRAF-mutant melanoma patients. Recent discovery of BRAF mutation in canine cancers underscores the importance of MAPK pathway activation as an oncogenic molecular alteration evolutionarily conserved between species. A comparative approach using the domestic dog as a spontaneous cancer model will provide new insights into the dysregulation of BRAF/MAPK pathway in carcinogenesis and facilitate in vivo studies to evaluate therapeutic strategies targeting this pathway’s molecules for cancer therapy. The BRAF mutation in canine cancers may also represent a molecular marker and therapeutic target in veterinary oncology. This review article summarizes the current knowledge on BRAF mutations in human and canine cancers and discusses the potential applications of this abnormality in veterinary oncology. Full article
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)
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Open AccessReview
Comparative Aspects of Osteosarcoma Pathogenesis in Humans and Dogs
Vet. Sci. 2015, 2(3), 210-230; https://doi.org/10.3390/vetsci2030210 - 17 Aug 2015
Cited by 14
Abstract
Osteosarcoma (OS) is a primary and aggressive bone sarcoma affecting the skeleton of two principal species, human beings and canines. The biologic behavior of OS is conserved between people and dogs, and evidence suggests that fundamental discoveries in OS biology can be facilitated [...] Read more.
Osteosarcoma (OS) is a primary and aggressive bone sarcoma affecting the skeleton of two principal species, human beings and canines. The biologic behavior of OS is conserved between people and dogs, and evidence suggests that fundamental discoveries in OS biology can be facilitated through detailed and comparative studies. In particular, the relative genetic homogeneity associated with specific dog breeds can provide opportunities to facilitate the discovery of key genetic drivers involved in OS pathogenesis, which, to-date, remain elusive. In this review, known causative factors that predispose to the development OS in human beings and dogs are summarized in detail. Based upon the commonalities shared in OS pathogenesis, it is likely that foundational discoveries in one species will be translationally relevant to the other and emphasizes the unique opportunities that might be gained through comparative scientific approaches. Full article
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)
Open AccessReview
Comparative Aspects of Molecular Mechanisms of Drug Resistance through ABC Transporters and Other Related Molecules in Canine Lymphoma
Vet. Sci. 2015, 2(3), 185-205; https://doi.org/10.3390/vetsci2030185 - 12 Aug 2015
Cited by 3
Abstract
The most important causes of treatment failure in canine lymphoma include intrinsic or acquired drug resistance. Thus, elucidation of molecular mechanisms of drug resistance is essential for the establishment of better treatment alternatives for lymphoma patients. The overexpression of drug transporters is one [...] Read more.
The most important causes of treatment failure in canine lymphoma include intrinsic or acquired drug resistance. Thus, elucidation of molecular mechanisms of drug resistance is essential for the establishment of better treatment alternatives for lymphoma patients. The overexpression of drug transporters is one of the most intensively studied mechanisms of drug resistance in many tumors. In canine lymphoma, it has also been shown that the overexpression of drug efflux pumps such as P-glycoprotein is associated with drug-resistant phenotypes. Canine lymphoma has many pathological similarities to human non-Hodgkin’s lymphoma, and they also share similar molecular mechanisms of drug resistance. We have previously demonstrated the association of the overexpression of drug transporters with drug resistance and indicated some molecular mechanisms of the regulation of these transporters’ expressions in canine and human lymphoid tumor cells. However, it has also been indicated that other known or novel drug resistance factors should be explored to overcome drug resistance in lymphoma. In this review, we summarize the recent findings on the molecular mechanisms of drug resistance and possible strategies to develop better treatment modalities for canine lymphoma from the comparative aspects with human lymphoid tumors. Full article
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)
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Open AccessReview
Mechanisms of Drug Resistance in Veterinary Oncology— A Review with an Emphasis on Canine Lymphoma
Vet. Sci. 2015, 2(3), 150-184; https://doi.org/10.3390/vetsci2030150 - 12 Aug 2015
Cited by 7
Abstract
Drug resistance (DR) is the major limiting factor in the successful treatment of systemic neoplasia with cytotoxic chemotherapy. DR can be either intrinsic or acquired, and although the development and clinical implications are different, the underlying mechanisms are likely to be similar. Most [...] Read more.
Drug resistance (DR) is the major limiting factor in the successful treatment of systemic neoplasia with cytotoxic chemotherapy. DR can be either intrinsic or acquired, and although the development and clinical implications are different, the underlying mechanisms are likely to be similar. Most causes for DR are pharmacodynamic in nature, result from adaptations within the tumor cell and include reduced drug uptake, increased drug efflux, changes in drug metabolism or drug target, increased capacity to repair drug‐induced DNA damage or increased resistance to apoptosis. The role of active drug efflux transporters, and those of the ABC‐transporter family in particular, have been studied extensively in human oncology and to a lesser extent in veterinary medicine. Methods reported to assess ABC‐transporter status include detection of the actual protein (Western blot, immunohistochemistry), mRNA or ABC‐transporter function. The three major ABC‐transporters associated with DR in human oncology are ABCB1 or P‐gp, ABCC1 or MRP1, and ABCG2 or BCRP, and have been demonstrated in canine cell lines, healthy dogs and dogs with cancer. Although this supports a causative role for these ABC‐transporters in DR cytotoxic agents in the dog, the relative contribution to the clinical phenotype of DR in canine cancer remains an area of debate and requires further prospective studies. Full article
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)
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Open AccessReview
The Establishment of the Pfizer-Canine Comparative Oncology and Genomics Consortium Biospecimen Repository
Vet. Sci. 2015, 2(3), 127-130; https://doi.org/10.3390/vetsci2030127 - 07 Jul 2015
Cited by 8
Abstract
The Canine Comparative Oncology and Genomics Consortium (CCOGC) was formed in 2004 in an effort to capitalize on the generation of a domestic dog genome sequence assembly [1], which created new opportunities to investigate canine cancers at the molecular level [2]. [...] Full article
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)
Open AccessReview
Cats, Cancer and Comparative Oncology
Vet. Sci. 2015, 2(3), 111-126; https://doi.org/10.3390/vetsci2030111 - 30 Jun 2015
Cited by 13
Abstract
Naturally occurring tumors in dogs are well-established models for several human cancers. Domestic cats share many of the benefits of dogs as a model (spontaneous cancers developing in an immunocompetent animal sharing the same environment as humans, shorter lifespan allowing more rapid trial [...] Read more.
Naturally occurring tumors in dogs are well-established models for several human cancers. Domestic cats share many of the benefits of dogs as a model (spontaneous cancers developing in an immunocompetent animal sharing the same environment as humans, shorter lifespan allowing more rapid trial completion and data collection, lack of standard of care for many cancers allowing evaluation of therapies in treatment-naïve populations), but have not been utilized to the same degree in the One Medicine approach to cancer. There are both challenges and opportunities in feline compared to canine models. This review will discuss three specific tumor types where cats may offer insights into human cancers. Feline oral squamous cell carcinoma is common, shares both clinical and molecular features with human head and neck cancer and is an attractive model for evaluating new therapies. Feline mammary tumors are usually malignant and aggressive, with the ‘triple-negative’ phenotype being more common than in humans, offering an enriched population in which to examine potential targets and treatments. Finally, although there is not an exact corollary in humans, feline injection site sarcoma may be a model for inflammation-driven tumorigenesis, offering opportunities for studying variations in individual susceptibility as well as preventative and therapeutic strategies. Full article
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)

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Open AccessAddendum
Addendum: Mazcko, C., et al. The Establishment of the Pfizer-Canine Comparative Oncology and Genomics Consortium Biospecimen Repository. Vet. Sci. 2015, 2, 127–130
Vet. Sci. 2015, 2(4), 406; https://doi.org/10.3390/vetsci2040406 - 06 Nov 2015
Abstract
The authors wish to make the following correction to their paper published in Veterinary Sciences [1]: [...] Full article
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)
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