Comparison of mucin-1 in human breast cancer and canine mammary gland tumor: a review study

Mucin-1 (MUC-1) is a transmembrane glycoprotein, which bears many similarities between dogs and humans. Since the existence of animal models is essential to understand the significant factors involved in breast cancer mechanisms, canine mammary tumors (CMTs) could be used as a spontaneously occurring tumor model for human studies. Accordingly, this review assessed the comparison of canine and human MUC-1 based on their diagnostic and therapeutic aspects and showed how comparative oncology approaches could provide insights into translating pre-clinical trials from human to veterinary oncology and vice versa which could benefit both humans and dogs.

Radioimmunotherapy Targeting IGF2R on Canine-Patient-Derived Osteosarcoma Tumors in Mice and Radiation Dosimetry in Canine and Pediatric Models

Background: Osteosarcoma (OS) has an overall patient survival rate of ~70% with no significant improvements in the last two decades, and novel effective treatments are needed. OS in companion dogs is phenotypically close to human OS, which makes a comparative oncology approach to developing new treatments for OS very attractive. We have recently created a novel human antibody, IF3 to IGF2R, which binds to this receptor on both human and canine OS tumors. Here, we evaluated the efficacy and safety of radioimmunotherapy with 177Lu-labeled IF3 of mice bearing canine-patient-derived tumors and performed canine and human dosimetry calculations. Methods: Biodistribution and microSPECT/CT imaging with 111In-IF3 was performed in mice bearing canine OS Gracie tumors, and canine and human dosimetry calculations were performed based on these results. RIT of Gracie-tumor-bearing mice was completed with 177Lu-IF3. Results: Biodistribution and imaging showed a high uptake of 111In-IF3 in the tumor and spleen. Dosimetry identified the tumor, spleen and pancreas as the organs with the highest uptake. RIT was very effective in abrogating tumor growth in mice with some spleen-associated toxicity. Conclusions: These results demonstrate that RIT with 177Lu-IF3 targeting IGF2R on experimental canine OS tumors effectively decreases tumor growth. However, because of the limitations of murine models, careful evaluation of the possible toxicity of this treatment should be performed via nuclear imaging and image-based dosimetry in healthy dogs before clinical trials in companion dogs with OS can be attempted.

A Study on the Relationship Between Tumor Size, Tumor Grade and Lymph Node Involvement in Canine Mammary Cancer: Simulation of Tumor Behavior in Human Breast Cancer

Background: In the last two decades, canine mammary cancer has played an essential role in human breast cancer research. There are various similarities between biological and clinical features of canine breast cancer and female breast cancer in many cases. Clinical studies and evaluation of prognostic factors in canine mammary cancer can increase reliability in generalizing results to human cancers. This study was performed in the direction of comparative oncology. Methods: We collected clinicopathological data of an invasive type of canine mammary carcinoma from clinical records and pathology reports. Age, tumor laterality, tumor size, lymph node status, and tumor grade were recorded, and the relationships between the parameters were evaluated using linear regression analysis. Results: Ninety-seven patients were included in the study, and the mean age was 10.06 ± 2.73 years. The left mammary gland was involved in 51% of cases, and pT2 was the most common tumor size. Lymph nodes were involved in 27% of patients, and 43% of tumors were grade I. Statistical analysis showed no relationship between tumor size and laterality with other clinicopathological features. However, there was a statistically significant relationship between tumor size and tumor grade, and lymph node status. As the tumor size increased, tumor grade and the risk of lymph node involvement raised. Conclusion: Similar results of this study to breast cancer in women show that canine mammary carcinoma is a suitable model in comparative oncology research. Dogs live shorter than humans so that researchers can get the results of treatment and perform survival rate assessments faster in clinical trials. By considering ethical principles, dogs with breast cancer may replace phases I and II of human clinical trials in some cancer types soon.

Long-term assessment of risk factors for canine tumors registered in Xi’an, China

Tumors are one of the leading causes to death in pet dogs among diseases. The tumor incidence of pet dogs has been increasing, raising widespread concern.The tumor incidence of pet dogs has been increasing, raising widespread concern. In this study, retrospective analysis was performed with 246 tumor cases registered in Xi’an Animal Hospital, Northwest A&F University from 2009 to 2018. Correlations of sex, age and breed with tumor incidences were evaluated. The results showed that reproductive system tumors occupied the highest proportion (39.84%), followed by cutaneous tumors (28.05%), digestive tumors (18.70%) and ocular tumor (4.47%). Among the reproductive system tumors, breast tumors are the most common tumor in female pet dogs, especially for Pekingese (11.43%). Female dogs with high susceptibility to breast tumors were at the ages of 6–18 years old. As far as cutaneous tumors were concerned, the male pet dogs at all ages, particularly Golden Retrievers (17.39%), showed a high incidence. By contrast, male Samoyed aged from 4 to 13 years had the highest incidence (15.22%) of digestive tumors. In addition, pet dogs with ocular tumors mainly happened at the ages of 0–1 years and 6–13 years. Collectively, our findings are significant to develop effective measures of medical surveillance for pet dogs’ health and will provide insights for comparative oncology.

Moving beyond conventional stratified analysis to assess the treatment effect in a comparative oncology study

In a comparative oncology study with progression-free or overall survival as the endpoint, the primary or key secondary analysis is routinely stratified by patients’ baseline characteristics when evaluating the treatment difference. The validity of a conventional strategy such as a stratified HR analysis depends on stringent model assumptions that are unlikely to be met in practice, especially in immunotherapy studies. Thus, the resulting summary is generally neither valid nor interpretable. This article discusses issues with conventional stratified analyses and presents alternatives using data from KEYNOTE-189, a recent immunotherapy trial for treating patients with metastatic, non-squamous, non-small-cell lung cancer.

MiRNAs in Canine and Human Osteosarcoma: A Highlight Review on Comparative Biomolecular Aspects

Osteosarcoma (OS) is the most frequent primary malignant tumor of bone in humans and animals. Comparative oncology is a field of study that examines the cancer risk and tumor progression across the species. The canine model is ideally suited for translational cancer research. The biological and clinical characteristics of human and canine OS are common to hypothesize as that several living and environmental common conditions shared between the two species can influence some etiopathogenetic mechanisms, for which the canine species represents an important model of comparison with the human species. In the canine and human species, osteosarcoma is the tumor of bone with the highest frequency, with a value of about 80–85% (in respect to all other bone tumors), a high degree of invasiveness, and a high rate of metastasis and malignancy. Humans and dogs have many genetic and biomolecular similarities such as alterations in the expression of p53 and in some types of microRNAs that our working group has already described previously in several separate works. In this paper, we report and collect new comparative biomolecular features of osteosarcoma in dogs and humans, which may represent an innovative update on the biomolecular profile of this tumor.