Search

Human mastocytosis are heterogeneous group of neoplastic diseases characterized by a different degree of uncontrolled mast cell (MC) proliferation and activation. Interestingly, human mastocytosis share several biological and clinical features with canine mast cell disorders, so called canine mast cell tumors (CMCTs). These CMCTs are the most common spontaneous cutaneous tumors found in dogs representing a valid model to study neoplastic mast cell disorders. It has been discovered that the pathological activation of c-Kit receptor (c-KitR), expressed by MCs, has been involved in the pathogenesis of neoplastic MC disorders. In this review we have focused on human mastocytosis in terms of: (i) epidemiology and classification; (ii) pathogenesis at molecular levels; (iii) clinical presentation. In addition, we have summarized animal models useful to study neoplastic MC disorders including CMCTs and murine transgenic models. Finally, we have revised therapeutic approaches mostly common in human and canine MCTs and novel tyrosine kinase inhibitors approved for CMCTs and recently translated in human clinical trials., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Masitinib mesylate (AB1010) is a novel potent and selective tyrosine kinase inhibitor, targeting mainly wild-type and mutated c-Kit receptor (c-KitR), Platelet Derived Growth Factor Receptor-alfa/beta (PDGFRa/ß), Lymphocyte-specific kinase (Lck), Lck/Yes-related protein (LYn), Fibroblast Growth Factor Receptor 3 (FGFR3) and Focal Adhesion Kinase (FAK). It is the first anticancer therapy approved in veterinary medicine for the treatment of unresectable canine mast cell tumors (CMCTs), harboring activating c-KitR mutations, at dose of 12.5mg/kg once daily. Considering its anti-proliferative action, principally given by inhibiting the MCs c-KitR anti-angiogenic pathway that leads cancer progression, and its role as chemosensitizer, masitinib is under clinical investigation in several human malignancies (Gastro-Intestinal Stromal Tumors, acute myeloid leukemia, systemic mastocytosis, pancreatic cancer, multiple myeloma, non-small cell lung cancer, melanoma, ovarian and prostate cancer), which are characterized by similar canine c-KIT proto-oncogene mutations. Here, we analyze masitinib structure activity, its pharmacokinetics compared to imatinib, the c-KitR pathway referring to the most frequent c-KIT mutations sensitive or resistant to this novel drug compared to imatinib, and masitinib safety profile. We, also, explore preclinical and clinical (completed and ongoing) trials with the aim to emphasize as this recent anti-angiogenic therapy, at first approved in CMCTs and, currently in development for the treatment of several human neoplasms, could be represent a milestone in translational oncology, in which the murine experimental model of cancer research could be integrated by canine spontaneous tumor model., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Soft tissue sarcomas (STS) are rare tumors with mesenchymal origin, accounting for 1% of all human cancer. Local control of STS can be obtained through the use of surgery and radiotherapy. In about 40% of these patients, disease will recur at distant sites, and of these more than 90% will die because of this aggressive malignancy. In advanced and/or metastatic STS patients treated with anthracycline-based regimen the median overall survival is about 12 months, and it has remained unchanged during the last 20 years. Clearly, this strongly suggests the need for discover more active compounds in STS, such as imatinib in GIST or dermatofibrosarcoma patients. In this paper we describe the crucial role of angiogenesis mechanisms in sarcomas development and progression. Consequentially, we focus on pazopanib, a novel multitargeted tyrosine kinase inhibitor with anti-angiogenic activity, mainly due to VEGFR2 pathway interference. We also analyze principal completed trials leading pazopanib approval in sarcomas pretreated patients., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Murine cancer models have been extremely useful for analyzing the biology of pathways involved in cancer initiation, promotion, and progression. Interestingly, several murine cancer models also exhibit heterogeneity, genomic instability and an intact immune system. However, they do not adequately represent several features that define cancer in humans, including long periods of latency, the complex biology of cancer recurrence and metastasis and outcomes to novel therapies. Therefore, additional models that better investigate the human disease are needed. In the pet population, with special references to the dog, cancer is a spontaneous disease and dogs naturally develop cancers that share many characteristics with human malignancies. More than 40 years ago, optimization of bone marrow transplantation protocols was undertaken in dogs and recently novel targeted therapies such as liposomal muramyl tripeptide phosphatidylethanolamine and several tyrosine kinase inhibitors, namely masitinib (AB1010) and toceranib phosphate (SU11654), have been developed to treat dog tumors which have then been translated to human clinical trials. In this review article, we will analyze biological data from dog tumors and comparative features with human tumors, and new therapeutic approaches translated from dog to human cancer., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The clinical application of the pure beta emitter (90)Y constitutes a fundamental advancement in non-invasive medicine. Nowadays, mainly three oncological therapies exploit the intrinsic emissive characteristic of (90)Y. Radionuclide therapies include peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumour (NET) treatment, radioimmunotherapy (RIT) in non-Hodgkin's lymphoma (NHL) treatment and transarterial radioembolization therapy (TARET) in unresectable hepatocellular carcinoma (HCC) and liver metastatic colorectal cancer (mCRC) treatment. The last ten years of clinical experience from E-PubMed research have been reviewed and an efficacy correlation between (90)Y-therapies has shown a better objective response rate for RIT (ORR 80±15%; range 53-100) compared to PRRT (ORR 23.5±14%; range 9-50), and TARET (ORR for mCRC, 40±25%; range 19-91, and ORR for HCC, 42±20%; range 20-82). This review reports on the state of the art of the efficacy of (90)Y-therapies from the last decade and discusses new perspectives of therapeutic development., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The liver is the primary site of metastases for many malignancies. Gastrointestinal cancers are especially prone to spread to the liver and other tumours, as breast cancer and melanoma often spread to the liver. On the other hand, hepatocellular cancer (HCC) is the fifth most common malignancy in the world due to its common etiology from chronic liver damage caused by hepatitis or cirrhosis. Treatments of liver tumours vary according to histology and liver invasion and until now trans-arterial chemoembolization (TACE) has represented a main approach in the therapy of liver tumours. This review takes into consideration: (i) the background to utilizing TACE in liver tumours; (ii) TACE methods and the biological rationale for utilizing chemotherapeutic agents coated to a new micro-particle such as DC-Beads and HepaSphere; (iii) clinical experiences employing TACE in different liver tumours; (iv) the pivotal role of angiogenesis and hypoxia-induced angiogenesis following TACE with special references to HCC. Finally, the rationale for the combination of TACE with angiogenesis inhibitors is also discussed., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)