title: 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.affiliation: Centre for Tumor Biology, Barts Cancer Institute-a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Ping-Pui
authors.initials: PP
authors.lastname: Wong
authors.affiliation: Centre for Tumor Biology, Barts Cancer Institute-a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Fevzi
authors.initials: F
authors.lastname: Demircioglu
authors.affiliation: Centre for Haemato-Oncology, Barts Cancer Institute-a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Essam
authors.initials: E
authors.lastname: Ghazaly
authors.affiliation: Centre for Molecular Oncology, Barts Cancer Institute-a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Wasfi
authors.initials: W
authors.lastname: Alrawashdeh
authors.affiliation: CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
authors.forename: Michael R L
authors.initials: MR
authors.lastname: Stratford
authors.affiliation: Mary Lyon Centre, MRC Harwell, Harwell Science and Innovation Campus, Oxfordshire OX11 0RD, UK.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Scudamore
authors.affiliation: Centre for Tumor Biology, Barts Cancer Institute-a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Biancastella
authors.initials: B
authors.lastname: Cereser
authors.affiliation: Centre for Molecular Oncology, Barts Cancer Institute-a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Crnogorac-Jurcevic
authors.affiliation: Centre for Tumor Biology, Barts Cancer Institute-a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: McDonald
authors.affiliation: Centre for Tumor Biology, Barts Cancer Institute-a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: George
authors.initials: G
authors.lastname: Elia
authors.affiliation: Centre for Cancer Inflammation, Barts Cancer Institute-a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK; Barts and the London HPB Centre, The Royal London Hospital, Barts Health NHS Trust, London E1 1BB, UK.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Hagemann
authors.affiliation: Centre for Tumor Biology, Barts Cancer Institute-a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK; Barts and the London HPB Centre, The Royal London Hospital, Barts Health NHS Trust, London E1 1BB, UK.
authors.forename: Hemant M
authors.initials: HM
authors.lastname: Kocher
authors.affiliation: Centre for Tumor Biology, Barts Cancer Institute-a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK. Electronic address: k.hodivala-dilke@qmul.ac.uk.
authors.forename: Kairbaan M
authors.initials: KM
authors.lastname: Hodivala-Dilke
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004357:Drug Synergism; D006801:Humans; D008168:Lung / Q000098:blood supply / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010179:Pancreas / Q000098:blood supply / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012910:Snake Venoms / Q000008:administration & dosage* / Q000627:therapeutic use; D014700:Verapamil / Q000008:administration & dosage* / Q000627:therapeutic use; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D012910:Snake Venoms; D003841:Deoxycytidine; C422910:Cilengitide; D014700:Verapamil; D000093542:Gemcitabine