Please cite this article in press as: Ranieri G, et al. Tyrosine kinase inhibitors (TKIs) in human and pet tumours with special reference to breast cancer: A comparative review. Crit Rev Oncol/Hematol (2013), http://dx.doi.org/10.1016/j.critrevonc.2013.05.009 ARTICLE IN PRESS ONCH-1740; No. of Pages 16 Critical Reviews in Oncology/Hematology xxx (2013) xxx–xxx Tyrosine kinase inhibitors (TKIs) in human and pet tumours with special reference to breast cancer: A comparative review Girolamo Ranieri a,* , Marianna Pantaleo b , Mariagrazia Piccinno b , Maria Roncetti b , Maddalena Mutinati b , Ilaria Marech c , Rosa Patruno d , Annalisa Rizzo b , Raffaele Luigi Sciorsci b a Interventional Radiology Unit with Integrated Section of Transational Medical Oncology National Cancer Research Centre, Cancer Institute“Giovanni Paolo II”, Bari, Italy b Department of Emergencies and Organ Transplantation (DETO)-University of Bari “Aldo Moro”, Italy c Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy d Department of Prevention and Animal Ealth, ASL BAT, Barletta, Italy Accepted 17 May 2013 Contents 1. Breast tumours in humans and pets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 2. Dysregulation of tyrosine kinase proteins in tumours . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 3. The TKR type III family and breast cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 3.1. PDGFRs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 3.2. Colony stimulating factor-1 receptor (CSF-1R, c-fms) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 3.3. c-KitR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 4. Tyrosine kinase inhibitors (TKIs) in the treatment of cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 4.1. EGFR and HER-2 inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 4.2. VEGFR, PDGFR, c-KitR and CSF-1R inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 5. Concluding remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Biographies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 Abstract Tyrosine kinase receptors (TKRs) play a key role in tumour cell proliferation and survival since they are involved in endothelial cell activation leading to tumour neoangiogenesis. In particular, vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptor (PDGFR), stem cell factor receptor (c-KitR), and colony-stimulating factor 1 (CSF-1) are overexpressed or constitutively activated in human and pet malignancies. A variety of small molecule inhibitors targeting specific tyrosine kinases (known as tyrosine kinase inhibitors or TKIs) have recently been approved, or are under investigation, for the treatment of human cancer. TKI application in animal * Corresponding author at: Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre “Giovanni Paolo II”, via Orazio Flacco 65, 70124, Bari, Italy. Tel.: +39 080 5555561; fax: +39 080 5555563. E-mail addresses: giroran@tiscalinet.it, girolamo.ranieri@libero.it (G. Ranieri). 1040-8428/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.critrevonc.2013.05.009