Simple Summary Cancer is a significant cause of suffering and death in domestic cats. In humans, an understanding of the genetics of different types of cancers has become clinically important for all aspects of patient care and forms the basis for most emerging diagnostics and therapies. The field of ‘oncogenomics’ characterises the alterations of cancer-associated genes that are found in tumours. Such a thorough understanding of the oncogenome of human tumours has only been possible due to a high-quality reference genome and an understanding of the genetic variation that can exist between people. Although a high-quality reference genome for cats has only recently been generated, investigations into understanding the genetics of feline cancers have been underway for many years, using a range of different technologies. This review summarises what is currently known of the genetics of both common and rare types of cancer in domestic cats. Drawing attention to our current understanding of the feline oncogenome will hopefully bring this topic into focus and serve as a springboard for more much-needed research into the genetics of cancer in domestic cats. Abstract Cancer is a significant cause of morbidity and mortality in domestic cats. In humans, an understanding of the oncogenome of different cancer types has proven critical and is deeply interwoven into all aspects of patient care, including diagnostics, prognostics and treatments through the application of targeted therapies. Investigations into understanding the genetics of feline cancers started with cytogenetics and was then expanded to studies at a gene-specific level, looking for mutations and expression level changes of genes that are commonly mutated in human cancers. Methylation studies have also been performed and together with a recently generated high-quality reference genome for cats, next-generation sequencing studies are starting to deliver results. This review summarises what is currently known of the genetics of both common and rare cancer types in cats, including lymphomas, mammary tumours, squamous cell carcinomas, soft tissue tumours, mast cell tumours, haemangiosarcomas, pulmonary carcinomas, pancreatic carcinomas and osteosarcomas. Shining a spotlight on our current understanding of the feline oncogenome will hopefully serve as a springboard for more much-needed research into the genetics of cancer in domestic cats.

/pdf/feline-oncogenomics-what-do-we-know-about-the-genetics-of-r0axgmya.pdf

Feline Oncogenomics: What Do We Know about the Genetics of Cancer in Domestic Cats?

While vascular endothelial growth factor receptor inhibitors (VEGFRis) have dramatically improved cancer survival, these drugs cause hypertension in a majority of patients. This side effect is often dose limiting and increases cardiovascular mortality in cancer survivors. This review summarizes recent advances in our understanding of the molecular mechanisms and clinical findings that impact management of VEGFRi-induced hypertension. Recent studies define new connections between endothelial dysfunction and VEGFRi-induced hypertension, including the balance between nitric oxide, oxidative stress, endothelin signaling, and prostaglandins and the potential role of microparticles, vascular smooth muscle cells, vascular stiffness, and microvessel rarefaction. Data implicating genetic polymorphisms that might identify patients at risk for VEGFRi-induced hypertension and the growing body of literature associating VEGFRi-induced hypertension with antitumor efficacy are reviewed. These recent advances have implications for the future of cardio-oncology clinics and the management of VEGFRi-induced hypertension. 

VEGF Receptor Inhibitor-Induced Hypertension: Emerging Mechanisms and Clinical Implications

Mast cell tumors (MCTs) are hematopoietic neoplasms composed of mast cells. It is highly common in dogs and is extremely important in the veterinary oncology field. It represents the third most common tumor subtype, and is the most common malignant skin tumor in dogs, corresponding to 11% of skin cancer cases. The objective of this critical review was to present the report of the 2nd Consensus meeting on the Diagnosis, Prognosis, and Treatment of Canine Cutaneous and Subcutaneous Mast Cell Tumors, which was organized by the Brazilian Association of Veterinary Oncology (ABROVET) in August 2021. The most recent information on cutaneous and subcutaneous mast cell tumors in dogs is presented and discussed.

/pdf/diagnosis-prognosis-and-treatment-of-canine-cutaneous-and-27ovn4dm.pdf

Diagnosis, Prognosis and Treatment of Canine Cutaneous and Subcutaneous Mast Cell Tumors

Prognostic factors in myelodysplastic syndromes

ObjectivesAlthough feline mammary carcinomas (FMCs) are highly metastatic, the literature and treatment options pertaining to advanced tumours are scarce. This study aimed to investigate the clinic...

Metastatic feline mammary cancer: prognostic factors, outcome and comparison of different treatment modalities – a retrospective multicentre study:

BACKGROUND Gastrointestinal stromal tumors (GISTs) are uncommon intestinal neoplasms in the dog. Literature regarding adjunctive therapy for GISTs in dogs is sparse. High-risk GISTs in humans respond to tyrosine kinase inhibition in the adjuvant setting. OBJECTIVES To review cases of toceranib phosphate use in dogs with GISTs and provide initial assessment of possible biological activity. A secondary aim was to evaluate patient and tumor characteristics for possible prognostic value. ANIMALS Twenty-seven dogs with confirmed GISTs based on histopathology and immunohistochemistry treated with toceranib. METHODS Retrospective study in which cases of toceranib use in dogs with GIST were solicited using the American College of Veterinary Internal Medicine Oncology and Small Animal Internal Medicine listservs. RESULTS Five of 7 dogs with gross disease experienced clinical benefit (71%; 3 complete responses, 1 partial response, 1 stable disease). These included 2 dogs with durable responses after toceranib discontinuation. Median progression-free interval (PFI) in dogs with gross disease was 110 weeks (range, 36-155 weeks). Median PFI in dogs with microscopic disease was 67 weeks (range, 9-257 weeks). Metastasis at diagnosis (P = 0.04) and high mitotic index (P < 0.001) were associated with shorter PFI in toceranib-treated dogs. CONCLUSIONS AND CLINICAL IMPORTANCE Biological activity of toceranib is evident in dogs with gross disease. Metastasis of GIST at diagnosis, as well as high tumor mitotic index, was associated with shorter PFI in toceranib-treated dogs. Larger studies are needed to define postsurgical risk and refine the use of toceranib in dogs with gross and microscopic GIST.

/pdf/retrospective-evaluation-of-toceranib-phosphate-palladia-use-5gnar9mo9l.pdf

Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of gastrointestinal stromal tumors of dogs.

Objectives The purpose of this study was to solicit and compile data from practicing veterinary specialists regarding their use of toceranib in cats with mast cell neoplasia and to provide initial assessment of possible clinical benefit and adverse events. Methods The American College of Veterinary Internal Medicine and Oncology listservs were used to solicit data pertaining to cases in which toceranib was used in the treatment of feline mast cell neoplasia. Cases were included if the following data were received: signalment (age, sex, breed), diagnosis of mast cell neoplasia by either cytology or histopathology, anatomic classification of disease (cutaneous, splenic/hepatic, gastrointestinal, other), previous and concurrent treatment, toceranib dose (mg/kg) and schedule, duration of therapy, best response and documentation of adverse events. Results Case data from 50 cats with cutaneous (n = 22), splenic/hepatic (visceral) (n = 10), gastrointestinal (n = 17) or other (n = 1) mast cell neoplasia were received. Clinical benefit was seen in 80% (40/50), including 86% (19/22) with cutaneous, 80% (8/10) with visceral and 76% (13/17) with gastrointestinal involvement. A majority of cats (n = 35) received glucocorticoids during toceranib treatment. Median duration of treatment in cats experiencing clinical benefit was 36 weeks (range 4-106 weeks), 48 weeks (range 12-199 weeks) and 23 weeks (range 13-81 weeks) for cutaneous, visceral and gastrointestinal cases, respectively. Toceranib was administered at a median dose of 2.5 mg/kg (range 1.6-3.5 mg/kg); in 90% (45/50) the drug was given three times per week. Treatment was generally well tolerated with 60% (30/50) of cats experiencing adverse events. The majority of these events were low-grade (grade 1 or 2) gastrointestinal or hematologic events that resolved with treatment break and/or dose adjustment. Conclusions and relevance Toceranib appears to be well tolerated in feline patients with mast cell neoplasia. Biologic activity of this drug is evident in the studied cats; however, further prospective studies are needed to elucidate fully its role in treatment of this disease.

Retrospective evaluation of toceranib phosphate (Palladia) use in cats with mast cell neoplasia

An 11-year-old, female, spayed labrador retriever was presented to the Iowa State University Oncology Service for evaluation of a rapidly expanding mass located near the right prescapular lymph node. A Patnaik grade I mast cell tumour (mitotic index 3  cells/µl, reference interval 0–0.75). The patient was diagnosed with a histologically low-grade, biologically high-grade cutaneous, metastatic mast cell tumour with paraneoplastic hypereosinophilia. Changes in the magnitude of peripheral hypereosinophilia frequently paralleled tumour response to treatment with multiple antineoplastic agents. Nine months after initiating chemotherapy, treatment was discontinued due to declining quality of life.

https://bvajournals.onlinelibrary.wiley.com/doi/pdf/10.1136/vetreccr-2017-000563

Marked paraneoplastic hypereosinophilia associated with a low-grade, metastatic canine mast cell tumour

An adult female spayed Golden Retriever previously diagnosed with lymphoblastic lymphoma was presented to the Iowa State University oncology service with severe thrombocytopenia (20,000 plts/μL, reference interval: 200,000-500,000 plts/μL). Through bone marrow aspiration and cytology, it was found that the patient’s megakaryocytes demonstrated marked anisocytosis, cytosolic hypogranulation, and nuclear hypolobulation, which are all abnormal morphological findings consistent with dysmegakaryocytopoiesis, a type of myelodysplastic syndrome. The myelodysplastic syndromes refer to a collection of conditions characterized by the dysplasia of one or more of the hematopoietic cell lineages. Primary myelodysplastic syndromes are idiopathic, whereas secondary myelodysplastic syndromes have been associated with infectious diseases, toxin exposure, and drug treatments, including chemotherapy. Specifically, cancer patients receiving high cumulative doses of antineoplastic agents may be at an increased risk of developing a secondary myelodysplastic syndrome. At the time of diagnosis of dysmegakaryocytopoiesis, the patient had received 33 doses of chemotherapy through a University of Wisconsin-Madison multidrug protocol for canine lymphoma. Due to this development, it was elected to suspend the patient’s chemotherapy and the dysmegakaryocytopoiesis resolved within 2 months. The fact that cessation of chemotherapy was sufficient in increasing the patient’s platelet count into the normal range, and that the patient had no evidence of any additional underlying predisposing diseases or exposures, suggests that the cumulative cytotoxic effects of the chemotherapy treatment led to the development of dysmegakaryocytopoiesis. To our knowledge, this is only the second report in the veterinary literature describing chemotherapy-induced selective dysmegakaryocytopoiesis.

/pdf/selective-dysmegakaryocytopoiesis-secondary-to-chemotherapy-eqzcb03173.pdf

Selective Dysmegakaryocytopoiesis Secondary to Chemotherapy in a Dog with Lymphoblastic Lymphoma: A Case Report

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Papers

Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of gastrointestinal stromal tumors of dogs.

Retrospective evaluation of toceranib phosphate (Palladia) use in cats with mast cell neoplasia

Marked paraneoplastic hypereosinophilia associated with a low-grade, metastatic canine mast cell tumour

Selective Dysmegakaryocytopoiesis Secondary to Chemotherapy in a Dog with Lymphoblastic Lymphoma: A Case Report