Dual-action combination therapy enhances angiogenesis while reducing tumor growth and spread.

Abstract

Increasing chemotherapy delivery to tumors, while enhancing drug uptake and reducing side effects, is a primary goal of cancer research. In mouse and human cancer models in vivo, we show that coadministration of low-dose Cilengitide and Verapamil increases tumor angiogenesis, leakiness, blood flow, and Gemcitabine delivery. This approach reduces tumor growth, metastasis, and minimizes side effects while extending survival. At a molecular level, this strategy alters Gemcitabine transporter and metabolizing enzyme expression levels, enhancing the potency of Gemcitabine within tumor cells in vivo and in vitro. Thus, the dual action of low-dose Cilengitide, in vessels and tumor cells, improves chemotherapy efficacy. Overall, our data demonstrate that vascular promotion therapy is a means to improve cancer treatment.

• Authors: Ping-Pui Wong, Fevzi Demircioglu, Essam Ghazaly, Wasfi Alrawashdeh, Michael R L Stratford, Cheryl L Scudamore, Biancastella Cereser, Tatjana Crnogorac-Jurcevic, Stuart McDonald, George Elia, Thorsten Hagemann, Hemant M Kocher, Kairbaan M Hodivala-Dilke
• Journal: Cancer cell (Cancer Cell) Vol. 27 Issue 1 Pg. 123-37 (Jan 12 2015) ISSN: 1878-3686 [Electronic] United States
• PMID: 25584895 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Antimetabolites, Antineoplastic
• Snake Venoms
• Deoxycytidine
• Cilengitide
• Verapamil
• Gemcitabine

Topics

• Animals
• Antimetabolites, Antineoplastic (administration & dosage, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols
• Carcinoma, Lewis Lung (drug therapy, pathology)
• Cell Line, Tumor
• Deoxycytidine (administration & dosage, analogs & derivatives, therapeutic use)
• Drug Synergism
• Humans
• Lung (blood supply, pathology)
• Mice
• Mice, Inbred C57BL
• Neoplasm Transplantation
• Neovascularization, Pathologic (drug therapy)
• Pancreas (blood supply, pathology)
• Pancreatic Neoplasms (drug therapy, pathology)
• Snake Venoms (administration & dosage, therapeutic use)
• Verapamil (administration & dosage, therapeutic use)
• Gemcitabine