A model of study for human cancer: Spontaneous occurring tumors in dogs. Biological features and translation for new anticancer therapies

Ranieri, Girolamo; Gadaleta, Cosmo Damiano; Patruno, Rosa; Zizzo, Nicola; Daidone, Maria Grazia; Hansson, Mats; Paradiso, Angelo; Ribatti, Doménico

doi:10.1016/j.critrevonc.2013.03.005

Cited by 109 publications

(71 citation statements)

References 74 publications

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“…Actually, naturally occurring lymphomas in dogs are closer to their human counterparts than any xenograft mice models, because of their growth over long periods of time in an intact immune system, interindividual and intratumoral heterogeneity, development of recurrent or resistant diseases, and metastasis (13). Clinical presentation, biologic behavior, tumor genetics, and treatment response are very similar between canine and human DLBCL (14,15). Moreover, recent gene profiling expression studies emphasized the molecular similarities of DLBCL in both species (16,17).…”

Section: Introductionmentioning

confidence: 99%

Phase I Clinical Pharmacology Study of F14512, a New Polyamine-Vectorized Anticancer Drug, in Naturally Occurring Canine Lymphoma

Tierny

Serres

Segaoula

et al. 2015

Clinical Cancer Research

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Purpose: F14512 is a new topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells and increases topoisomerase II poisoning. F14512 is currently in a phase I/II clinical trial in patients with acute myeloid leukemia. The aim of this study was to investigate F14512 potential in a new clinical indication. Because of the many similarities between human and dog lymphomas, we sought to determine the tolerance, efficacy, pharmacokinetic/pharmacodynamic (PK/PD) relationship of F14512 in this indication, and potential biomarkers that could be translated into human trials. Experimental Design: Twenty-three dogs with stage III–IV naturally occurring lymphomas were enrolled in the phase I dose-escalation trial, which consisted of three cycles of F14512 i.v. injections. Endpoints included safety and therapeutic efficacy. Serial blood samples and tumor biopsies were obtained for PK/PD and biomarker studies. Results: Five dose levels were evaluated to determine the recommended dose. F14512 was well tolerated, with the expected dose-dependent hematologic toxicity. F14512 induced an early decrease of tumoral lymph node cells, and a high response rate of 91% (21/23) with 10 complete responses, 11 partial responses, 1 stable disease, and 1 progressive disease. Phosphorylation of histone H2AX was studied as a potential PD biomarker of F14512. Conclusions: This trial demonstrated that F14512 can be safely administered to dogs with lymphoma resulting in strong therapeutic efficacy. Additional evaluation of F14512 is needed to compare its efficacy with standards of care in dogs, and to translate biomarker and efficacy findings into clinical trials in humans. Clin Cancer Res; 21(23); 5314–23. ©2015 AACR.

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Section: Introductionmentioning

confidence: 99%

Phase I Clinical Pharmacology Study of F14512, a New Polyamine-Vectorized Anticancer Drug, in Naturally Occurring Canine Lymphoma

Tierny

Serres

Segaoula

et al. 2015

Clinical Cancer Research

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“…There is no "gold standard" treatment for many canine cancers and so it is possible to evaluate new agents as firstline therapies, in combination with other treatments, or as adjunctive therapies in an expedited and efficient manner [41]. Moreover, as several cancer-associated genetic alterations that influence cancer progression in humans have been identified in canine cancer [36,42,43], testing new targeted therapies for cancer treatment holds great translational value for proof-of-concept and proof-of-target efficacy. Naturally occurring tumors develop over long periods and constantly interact with the syngeneic immune system of the canine patients, shaping the immune response and the immune environment and mimicking the natural cancer immunoediting of human patients.…”

Section: Similarities Between Human and Pet Tumorsmentioning

confidence: 99%

The importance of comparative oncology in translational medicine

Riccardo

Aurisicchio²,

Impellizeri³

et al. 2014

Cancer Immunol Immunother

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“…Some canine cancers that have been studied as models of analogous human disease include breast, prostate, bladder, and head and neck cancer, as well as osteosarcoma, lymphoma, and malignant melanoma (9, 10). These naturally-occurring neoplastic diseases in companion animals offer significant advantages over more traditional in vivo models of induced neoplastic disease including similarities in terms of etiology, heterogeneity, biological and metastatic behavior, and clinical response to therapy than does a cancer induced in a laboratory animal with an incompetent immune system (9)(10)(11)(12). Many of these advantages are outlined in Table 1.…”

Section: The Role For Companion Animal Models In Cancer Nanomedicine mentioning

confidence: 99%

Unleashing the power of comparative oncology models in nanomedicine research

Henry

2015

European Journal of Nanomedicine

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Abstract:The pathway from discovery of novel candidate drugs, including nanomedicine compounds, to FDA approval is lengthy and may be difficult to navigate. Oftentimes, investigational drugs are appropriately abandoned early in the development pathway due to preclinical failure. Other novel compounds may look quite promising in rodent models and preclinical trials, but prove disappointing when tested in human patients. In fact, only 5% of drugs entering Phase I human cancer clinical trials in the US are ultimately approved. Given the enormous cost, in terms of both financial investment and delay in progress toward improved patient outcome, there is a critical need for a more reliable and efficient process. One solution may be to improve translatability of our preclinical data by including trials in cancer-bearing pet dogs in the drug development pathway.

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A model of study for human cancer: Spontaneous occurring tumors in dogs. Biological features and translation for new anticancer therapies

Cited by 109 publications

References 74 publications

Phase I Clinical Pharmacology Study of F14512, a New Polyamine-Vectorized Anticancer Drug, in Naturally Occurring Canine Lymphoma

Phase I Clinical Pharmacology Study of F14512, a New Polyamine-Vectorized Anticancer Drug, in Naturally Occurring Canine Lymphoma

The importance of comparative oncology in translational medicine

Unleashing the power of comparative oncology models in nanomedicine research

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