Exploring new biomarkers in the tumour microenvironment of canine inflammatory mammary tumours

Raposo, Teresa P; Pires, Isabel; Prada, Justina; Queiroga, Felisbina L.; Argyle, David

doi:10.1111/vco.12209

Cited by 23 publications

(17 citation statements)

References 52 publications

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“…Toceranib targets, among others, VEGF; thus, an anti‐angiogenic effect has to be expected for tumours expressing high levels of this molecule, including IMC …”

Section: Discussionmentioning

confidence: 99%

“…Toceranib targets, among others, VEGF; thus, an anti-angiogenic effect has to be expected for tumours expressing high levels of this molecule, including IMC. [9][10][11][12] It is currently unknown whether the combination of piroxicam, thalidomide and toceranib enhanced anti-angiogenic effect compared with either agent alone.…”

Section: Discussionmentioning

confidence: 99%

“…Toceranib phosphate (Palladia) is a multitargeted tyrosine kinase inhibitor with activity against Kit, VEGFR2, PDGFR alfa and PDGFR beta. As IMC expresses vascular VEGF or has aberrant VEGF signalling, toceranib has the potential to be active against this tumour . Toceranib also produces a significant decrease in regulatory T‐cells, which may increase immune surveillance …”

Section: Introductionmentioning

confidence: 99%

“…As IMC expresses vascular VEGF or has aberrant VEGF signalling, toceranib has the potential to be active against this tumour. [9][10][11][12] Toceranib also produces a significant decrease in regulatory T-cells, which may increase immune surveillance. 13 IMC is a highly angiogenic and lymphangiogenic tumour, that is also characterized by a phenomenon known as vasculogenic mimicry, consisting in de novo generation of microvascular channels by genetically deregulated tumour cells without endothelial cell participation.…”

Section: Introductionmentioning

confidence: 99%

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The impact of toceranib, piroxicam and thalidomide with or without hypofractionated radiation therapy on clinical outcome in dogs with inflammatory mammary carcinoma

Rossi

Sabattini

Vascellari

et al. 2018

Vet Comparative Oncology

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In dogs, inflammatory mammary carcinoma is a clinicopathological entity characterized by rapid progression and aggressive behavior from onset of disease. Reported median survival time is short, with no effective treatment options. The aims of this prospective, noncontrolled clinical trial were to investigate outcome variables and safety profile of toceranib, thalidomide and piroxicam with or without hypofractionated radiation therapy in dogs with measurable histologically confirmed inflammatory mammary carcinoma that underwent a complete staging. Eighteen dogs were enrolled: 14 received medical treatment, and 4 were treated with hypofractionated radiation therapy and medical therapy. Overall, median time to progression was 34 days and median survival time was 109 days. In dogs treated with medical therapy, overall response rate was 21%, and clinical benefit rate (CBR) was 64%; median time to progression was 28 days and median survival time was 59 days. In dogs receiving medical therapy and undergoing radiation therapy, overall response rate and clinical benefit rate were 100%, with significantly longer time to progression (156 days) and survival time (180 days). Overall, treatment was well tolerated, with mild gastrointestinal and dermatological adverse events. Although the optimal treatment to this disease remains uncertain, the current approach consisting of systemic anti-angiogenic drugs with or without hypofractionated radiation therapy, provided clinical benefit in a significant proportion of dogs and should, therefore, be further explored.

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“…Toceranib targets, among others, VEGF; thus, an anti‐angiogenic effect has to be expected for tumours expressing high levels of this molecule, including IMC …”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The impact of toceranib, piroxicam and thalidomide with or without hypofractionated radiation therapy on clinical outcome in dogs with inflammatory mammary carcinoma

Rossi

Sabattini

Vascellari

et al. 2018

Vet Comparative Oncology

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“…In addition, canines are a promising model for human cancers, as they age faster than humans but share the same environments and have high levels of phenotypic diversity [3]. Raposo and colleagues emphasized that canine inflammatory mammary carcinoma (CIMC) can serve as a very good model of human inflammatory breast cancer (IBC) [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms of Canine Cancers

Cao¹,

Kouznetsova²,

Tsigelny³

2019

obm genet

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Cancer is the leading cause of death in dogs, and 50 percent of dogs over the age of 10 develop cancer at some point. The most common cancers in dogs include lymphoma, mast cell tumors, osteosarcoma, mammary gland tumors, and melanoma, and many of them share marked similarities with their human counterparts. Although canines are afflicted with many of the same types of cancers as humans, the genetic basis behind these cancers are not as well understood. Thus, the aim of this study is to elucidate some of the molecular mechanisms behind canine cancers. Canine lymphoma mutation patterns generally vary with the type of lymphoma afflicted-B-cell lymphomas have mutations in the alternative NF-kB pathway including MAP3K14, whereas in T-cell lymphomas the mTOR pathway in boxers and cellular metabolism genes in golden retrievers are affected. Mast cell tumors are largely traced to internal tandem duplications and deletions in the juxtamembrane domain of the proto-oncogene c-KIT. In osteosarcoma, mutations in RB1 and TP53 (especially G: C->A:T transitions in exons 4 and 5), as well as CDK4 inhibitors CDKN2A/B are common. Mammary gland tumors are associated with BRCA2 underexpression due to reading frame shift and mutations in BRC repeat 3. Lastly, deletion or underexpression of p16 and PTEN and altered expression of cell-cell adhesion molecules are common factors in the development of melanoma. The genes identified were then studied to identify more key amino acid mutations that changed protein products and promoted tumorigenesis. Genes that altered expression levels of proteins were analyzed separately. Both sets of candidate genes were then analyzed with the Database for Annotation, Visualization, and Integrated Discovery (DAVID) in order to elucidate the molecular pathways involved in canine cancers and identify more genes possibly involved in tumorigenesis. The proposition of this review is that treatments for both canine and human cancers would be enhanced by comparative genomic studies.

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