This review highlights therapeutic agents from recent cancer therapeutic trials showing the greatest potential for further clinical use for sunitinib in the near future. In fact, sunitinib is one of multi-tyrosine kinase inhibitors; tyrosine kinases are enzymes, which transfer phosphate groups from ATP to the hydroxyl group of tyrosine residues on signal transduction molecules. Phosphorylation of signal transduction molecules, in turn, induces dramatic changes in tumor growth, including activation of angiogenesis and DNA synthesis. Therefore, sustain efforts have been directed for developing inhibitors for angiogenesis, which is the marginal process for tumor growth and development through targeting TKs. Almost if not all angiogenesis inhibitors target the vascular endothelial growth factor (VEGF) signaling pathway.
M. E. Cockman, N. Masson, D. R. Mole, P. Jaakkola, G. W. Chang, S. C. Clifford, E. R. Maher, C. W. Pugh, P. J. Ratcliffe and P. H. Maxwell, “Hypoxia Inducible Factor-Alpha Binding and Ubiquitylation by the Von Hippel-Lindau Tumor Suppressor Protein,” Journal of Biological Chemistry, Vol. 275, No. 33, 2000, pp. 25733-25741. doi:10.1074/jbc.M002740200
D. W. Kim, Y. S. Jo, H. S. Jung, H. K. Chung, J. H. Song, K. C. Park, S. H. Park, J. H. Hwang, S. Y. Rha, G. R. Kweon, S. J. Lee, K. W. Jo and M. Shong, “An Orally Administered Multitarget Tyrosine Kinase Inhibitor, SU11248, Is a Novel Potent Inhibitor of Thyroid Oncogenic RET/Papillary Thyroid Cancer Kinases,” Journal of Clinical Endocrinology & Metabolism, Vol. 91, No. 10, 2006, pp. 4070-4076. doi:10.1210/jc.2005-2845
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K. J. Gotink and H. M. W. Verheul, “Anti-Angiogenic Tyrosine Kinase Inhibitors: What Is Their Mechanism of Action?” Angiogenesis, Vol. 13, No. 1, 2010, pp. 1-14. doi:10.1007/s10456-009-9160-6
R. H. Gunby, E. Sala, C. J. Tartari, M. Puttini, C. Gambacorti-Passerini and L. Mologni, “Oncogenic Fusion Tyrosine Kinases as Molecular Targets for Anti-Cancer Therapy,” Anti-Cancer Agents in Medicinal Chemistry, Vol. 7, No. 6, 2007, pp. 594-611. doi:10.2174/187152007784111340
T. J. Abrams, L. J. Murray, E. Pesenti, V. W. Holway, T. Colombo, L. B. Lee, J. M. Cherrington and N. K. Pryer, “Preclinical Evaluation of the Tyrosine Kinase Inhibitor SU11248 as a Single Agent and in Combination with “Standard of Care” Therapeutic Agents for the Treatment of Breast Cancer,” Molecular Cancer Therapeutics, Vol. 2, No. 10, 2003, pp. 1011-1021.
D. W. Kim, Y. S. Jo, H. S. Jung, H. K. Chung, J. H. Song, K. C. Park, S. H. Park, J. H. Hwang, S. Y. Rha, G. R. Kweon, S. J. Lee, K. W. Jo and M. Shong, “An Orally Administered Multitarget Tyrosine Kinase Inhibitor, SU-11248, Is a Novel Potent Inhibitor of Thyroid Oncogenic RET/Papillary Thyroid Cancer Kinases,” Clinical Endocrinology & Metabolism, Vol. 91, No. 10, 2006, pp. 4070-4076. doi:10.1210/jc.2005-2845
D. B. Mendel, A. D. Laird, X. Xin, S. G. Louie, J. G. Christensen, et al, “In Vivo Antitumor Activity of SU11248, a Novel Tyrosine Kinase Inhibitor Targeting Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor Receptors: Determination of a Pharmacokinetic/Pharmacodynamic Relationship,” Clinical Cancer Research, Vol. 9, No.1, 2003, pp. 327-337.
D. J. Hicklin and L. M. Ellis, “Role of the Vascular Endothelial Growth Factor Pathway in Tumor Growth and Angiogenesis,” Journal of Clinical Oncology, Vol. 23, No. 5, 2005, pp. 1011-1027.
U. McDermott, R. Y. Ames, A. J. Iafrate, S. Maheswaran, H. Stubbs, P. Greninger, K. McCutcheon, R. Milano, S. Y. Rha, A. Tam, D. Y. Lee, L. Lucien, B. W. Brannigan, L. E. Ulkus, X. J. Ma, M. G. Erlander, D. A. Haber, S. V. Sharma and J. Settleman, “Ligand-Dependent Platelet-Derived Growth Factor Receptor (PDGFR)-Alpha Activation Sensitizes Rare Lung Cancer and Sarcoma Cells to PDGFR Kinase Inhibitors,” Cancer Research, Vol. 69, No. 9, 2009, pp. 3937-3946. doi:10.1158/0008-5472.CAN-08-4327
J. O. Haznedar, S. Patyna, C. L. Bello, G. W. Peng, W. Speed, X. Yu, Q. Zhang, J. Sukbuntherng, D. J. Sweeny, L. Antonian and E. Y. Wu, “Single- and Multiple-Dose Disposition Kinetics of Sunitinib Malate, a Multitargeted Receptor Tyrosine Kinase Inhibitor: Comparative Plasma Kinetics in Non-Clinical Species,” Cancer Chemotherapy & Pharmacology, Vol. 64, No. 4, 2009, pp. 691-706. doi:10.1007/s00280-008-0917-1
H. Xin, C. Zhang, A. Herrmann, Y. Du, R. Figlin and H. Yu, “Sunitinib Inhibition of Stat3 Induces Renal Cell Carcinoma Tumor Cell Apoptosis and Reduces Immunosuppressive Cells,” Cancer Research, Vol. 69, No. 6, 2009, pp. 2506-2513. doi:10.1158/0008-5472.CAN-08-4323
B. Barré, A. Vigneron, N. Perkins, I. B. Roninson, E. Gamelin and O. Coqueret, “The STAT3 Oncogene as a Predictive Marker of Drug Resistance,” Trends in Molecular Medicine, Vol. 13, No. 1, 2007, pp. 4-11. doi:10.1016/j.molmed.2006.11.001
N. P. van Erp, K. Eechoute, A. A. van der Veldt, J. B. Haanen, A. K. Reyners, R. H. Mathijssen, E. Boven, T. van der Straaten, R. F. Baak-Pablo, J. A. Wessels, H. J. Guchelaar and H. Gelderblom, “Pharmacogenetic Pathway Analysis for Determination of Sunitinib-Induced Toxicity,” Journal of Clinical Oncology, Vol. 27, No. 26, 2009, pp. 4406-4412. doi:10.1200/JCO.2008.21.7679
C. L. Bello, L. Sherman, J. Zhou, L. Verkh, J. Smeraglia, J. Mount and K. J. Klamerus, “Effect of Food on the Pharmacokinetics of Sunitinib Malate (SU11248), a Multi-targeted Receptor Tyrosine Kinase Inhibitor: Results from a Phase I Study in Healthy Subjects,” Anticancer Drugs, Vol. 17, No. 3, 2006, pp. 353-358. doi:10.1097/00001813-200603000-00015
SUTENT (Sunitinib Malate) Prescribing Information, New York, Pfizer Labs.
V. L. Goodman, E. P. Rock, R. Dagher, R. P. Ramchandani, S. Abraham, J. V. Gobburu, B. P. Booth, S. L. Verbois, D. E. Morse, C. Y. Liang, N. Chidambaram, J. X. Jiang, S. Tang, K. Mahjoob, R. Justice and R. Pazdur, “Approval Summary: Sunitinib for the Treatment of Imatinib Refractory or Intolerant Gastrointestinal Stromal Tumors and Advanced Renal Cell Carcinoma,” Clinical Cancer Research, Vol. 13, No. 5, 2007, pp. 1367-1373. doi:10.1158/1078-0432.CCR-06-2328
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Pfizer Labs, Division of Pfizer Inc New York, 2010.
B. E. Houk, C. L. Bello, D. Kang and M. Amantea, “A Population Pharmacokinetic Meta-Analysis of Sunitinib Malate (SU11248) and Its Primary Metabolite (SU12662) in Healthy Volunteers and Oncology Patients,” Clinical Cancer Research, Vol. 15, No. 7, 2009, pp. 2497-2506. doi:10.1158/1078-0432.CCR-08-1893
K. M. Sakamoto, “Su-11248 Sugen,” Current Opinion in Investigational Drugs, Vol. 5, No. 12, 2004, pp. 1329-1339.
N. P. van Erp, S. D. Baker, A. S. Zandvliet, B. A. Ploeger, M. den Hollander, Z. Chen, J. den Hartigh, J. M. Konig-Quartel, H. J. Guchelaar and H. Gelderblom, “Marginal Increase of Sunitinib Exposure by Grapefruit Juice,” Cancer Chemotherapy and Pharmacology, Vol. 67, No. 3, 2010, pp. 695-703. doi:10.1007/s00280-010-1367-0
A. Italiano and B. Bui, “Gastrointestinal Stromal Tumors: Molecular Aspects and Therapeutic Implications,” Bull Cancer, Vol. 95, No. 1, 2008, pp. 107-116.
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J. O. Lee, K. W. Lee, C. J. Kim, Y. J. Kim, H. E. Lee, H. Kim, J. H. Kim, S. M. Bang, J. S. Kim and J. S. Lee, “Metastatic Adrenocortical Carcinoma Treated with Sunitinib: A Case Report” Japanese Journal of Clinical Oncology, Vol. 39,No. 8, 2009, pp. 183-185.
M. Palmowski, J. Huppert, P. Hauff, M. Reinhardt, K. Schreiner, M. A. Socher, P. Hallscheidt, G. Kauffmann, W. Semmler and F. Kiessling, “Vessel Fractions in Tumor Xenografts Depicted by Flow- or Contrast-Sensitive Three-Dimensional High-Frequency Doppler Ultrasound Respond Differently to Antiangiogenic Treatment,” Cancer Research, Vol. 68, No. 17, 2008, pp. 7042-7049. doi:10.1158/0008-5472.CAN-08-0285
C. L. Dai, Y. J. Liang, Y. S. Wang, A. K. Tiwari, Y. Y. Yan, F. Wang, Z. S. Chen, X. Z. Tong and L. W. Fu, “Sensitization of ABCG2-Overexpressing Cells to Conventional Chemotherapeutic Agent by Sunitinib Was Associated with Inhibiting the Function of ABCG2,” Cancer Letters, Vol. 279, No. 1, 2009, pp. 74-83. doi:10.1016/j.canlet.2009.01.027
C. J. Sweeney, E. G. Chiorean, C. F. Verschraegen, F. C. Lee, S. Jones, M. Royce, L. Tye, K. F. Liau, A. Bello, R. Chao and H. A. Burris, “A Phase I Study of Sunitinib Plus Capecitabine in Patients with Advanced Solid Tumors,” Journal of Clinical Oncology, Vol. 28, No. 28, 2010, pp. 4513-4520. doi:10.1200/JCO.2009.26.9696
E. Boven, C. Massard, J. P. Armand, C. Tillier, V. Hartog, N. M. Brega, A. M. Countouriotis, A. Ruiz-Garcia and J. C. Soria, “A Phase I, Dose-Finding Study of Sunitinib In Combination with Irinotecan in Patients with Advanced Solid Tumours,” British Journal of Cancer, Vol. 103, No. 7, 2010, pp. 993-1000. doi:10.1038/sj.bjc.6605852
N. Suhail, N. Bilal, H. Y. Khan, S. Hasan, S. Sharma, F. Khan, T. Mansoor and N. Banu, “Effect of Vitamins C and E on Antioxidant Status of Breast-Cancer Patients Undergoing Chemotherapy,” Journal of Clinical Pharmacy and Therapeutics, 2011, Online Version of Record Published before Inclusion in an Issue. doi:10.1111/j.1365-2710.2010.01237.x
K. Tikoo, M. S. Sane and C. Gupta, “Tannic Acid Ameliorates Doxorubicin-Induced Cardiotoxicity and Potentiates Its Anti-Cancer Activity: Potential Role of Tannins in Cancer Chemotherapy,” Toxicology and Applied Pharmacology, Vol. 251, No. 3, 2011, pp. 191-200. doi:10.1016/j.taap.2010.12.012
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A. Dahan, H. Sabit and G. L. Amidon, “The H2 Receptor Antagonist Nizatidine Is a P-Glycoprotein Substrate: Characterization of Its Intestinal Epithelial Cell Efflux Transport,” AAPS Journal, Vol. 11, No. 2, 2009, pp. 205- 213. doi:10.1208/s12248-009-9092-5
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