Tumor endothelial markers as a target in cancer

Introduction: Several anti-angiogenic agents have been developed and some of them have been clinically applied in the tumor therapy. Anti-angiogenic therapy faces some hurdles: inherent or acquired resistance, increased invasiveness, and lack of biomarkers. Characterization of tumor endothelial markers may help to target endothelium and to identify potential predictive factors of response to anti-angiogenic therapies. Numerous surrogates, angiogenic and endothelium markers have emerged from recent pre-clinical studies, including physiological and soluble molecules in plasma and from platelets, circulating cells, tumor tissue factors and imaging markers. However, no wholly validated biomarkers currently exist to predict the success or the failure of the anti-angiogenic therapy of cancer. Therefore, the research of suitable and validate biomarkers is currently ongoing. Areas covered: This review provides an overview of the status of our knowledge concerning tumor endothelial markers, therapeutics targeting, possible resistance mechanisms and predictive value of these biomarkers and discuss future strategies to use and identify them in the anti-angiogenic therapy. Expert opinion: Anti-angiogenesis is a milestone to improve the treatment of several types of cancer and predictive biomarkers for a response to anti-endothelium therapy are one of the most important challenges for anti-angiogenesis research.

[1]  Kerry A Chester,et al.  Antibody–drug conjugates – a perfect synergy , 2012, Expert opinion on biological therapy.

[2]  D. Neri,et al.  Antibody-drug conjugates: basic concepts, examples and future perspectives. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[3]  D. Arosio,et al.  Integrin-mediated drug delivery in cancer and cardiovascular diseases with peptide-functionalized nanoparticles. , 2012, Current medicinal chemistry.

[4]  J. Tibbitts,et al.  Pharmacokinetic Considerations for Antibody Drug Conjugates , 2012, Pharmaceutical Research.

[5]  J. Soria,et al.  Vascular disrupting agents: a delicate balance between efficacy and side effects , 2012, Current opinion in oncology.

[6]  E. Dejana,et al.  Vascular endothelial-cadherin and vascular stability , 2012, Current opinion in hematology.

[7]  V. Torchilin,et al.  Liposomes for cardiovascular targeting. , 2012, Therapeutic delivery.

[8]  D. Ribatti,et al.  Intussusceptive microvascular growth in tumors. , 2012, Cancer letters.

[9]  E. Papadimitriou,et al.  Pleiotrophin expression and role in physiological angiogenesis in vivo: potential involvement of nucleolin , 2012, Vascular cell.

[10]  Rongfu Wang,et al.  A concise review of current radiopharmaceuticals in tumor angiogenesis imaging. , 2012, Current pharmaceutical design.

[11]  R. Parhi,et al.  Preparation and characterization of solid lipid nanoparticles-a review. , 2012, Current drug discovery technologies.

[12]  P. LoRusso,et al.  Vascular disrupting agents (VDA) in oncology: advancing towards new therapeutic paradigms in the clinic. , 2011, Current drug targets.

[13]  A. Bobkov,et al.  Targeted drug delivery to tumor vasculature by a carbohydrate mimetic peptide , 2011, Proceedings of the National Academy of Sciences.

[14]  L. Vecchia,et al.  Targeted Drug Delivery Using Immunoconjugates: Principles and Applications , 2011, Journal of immunotherapy.

[15]  Angelo Corti,et al.  Tumor vasculature targeting through NGR peptide-based drug delivery systems. , 2011, Current pharmaceutical biotechnology.

[16]  Xin Yang,et al.  Molecular Imaging in Tumor Angiogenesis and Relevant Drug Research , 2011, Int. J. Biomed. Imaging.

[17]  J. Stafford,et al.  Increased exposure of phosphatidylethanolamine on the surface of tumor vascular endothelium. , 2011, Neoplasia.

[18]  L. Ricci-Vitiani,et al.  Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells , 2011, Nature.

[19]  Rong Wang,et al.  Glioblastoma stem-like cells give rise to tumour endothelium , 2010, Nature.

[20]  R. Weissleder,et al.  Targeted nanoagents for the detection of cancers , 2010, Molecular oncology.

[21]  R. Sidman,et al.  Phage display technology for stem cell delivery and systemic therapy. , 2010, Advanced drug delivery reviews.

[22]  Georgia Panagiotakos,et al.  Inhibition of Notch Signaling in Glioblastoma Targets Cancer Stem Cells via an Endothelial Cell Intermediate , 2010, Stem cells.

[23]  L. Borsig,et al.  Selectins promote tumor metastasis. , 2010, Seminars in cancer biology.

[24]  Minhong Yan,et al.  Chronic DLL4 blockade induces vascular neoplasms , 2010, Nature.

[25]  Teicher Ba.  Antibody-drug conjugate targets. , 2009 .

[26]  B. Geoerger,et al.  High Levels of Circulating VEGFR2+ Bone Marrow–Derived Progenitor Cells Correlate with Metastatic Disease in Patients with Pediatric Solid Malignancies , 2009, Clinical Cancer Research.

[27]  S. Rafii,et al.  SURROGATE MARKERS PREDICT ANGIOGENIC POTENTIAL AND SURVIVAL IN PATIENTS WITH GLIOBLASTOMA MULTIFORME , 2009, Neurosurgery.

[28]  T. Yip,et al.  Platelets actively sequester angiogenesis regulators. , 2009, Blood.

[29]  D. Kuik,et al.  Increased numbers of small circulating endothelial cells in renal cell cancer patients treated with sunitinib , 2009, Angiogenesis.

[30]  B. Teicher.  Antibody-drug conjugate targets. , 2009, Current cancer drug targets.

[31]  F. Bertolini,et al.  Circulating endothelial cells as biomarkers for angiogenesis in tumor progression. , 2009, Frontiers in bioscience.

[32]  D. Ribatti,et al.  Enhanced Antitumor Efficacy of Clinical-Grade Vasculature-Targeted Liposomal Doxorubicin , 2008, Clinical Cancer Research.

[33]  G. Ahn,et al.  Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: role of bone marrow-derived myelomonocytic cells. , 2008, Cancer cell.

[34]  T. Yip,et al.  Platelet-associated PF-4 as a biomarker of early tumor growth. , 2008, Blood.

[35]  D. Nolan,et al.  Endothelial Progenitor Cells Control the Angiogenic Switch in Mouse Lung Metastasis , 2008, Science.

[36]  A. Nassef,et al.  Serum Soluble Vascular Cell Adhesion Molecule-1 ( sVCAM-1 ) in Acute Ischemic Stroke , 2008 .

[37]  H. Shmeeda,et al.  An open-label study to evaluate dose and cycle dependence of the pharmacokinetics of pegylated liposomal doxorubicin , 2008, Cancer Chemotherapy and Pharmacology.

[38]  S. Rabbani,et al.  Binding and internalization of NGR-peptide-targeted liposomal doxorubicin (TVT-DOX) in CD13-expressing cells and its antitumor effects , 2007, Anti-cancer drugs.

[39]  W. Arap,et al.  Molecular targets on blood vessels for cancer therapies in clinical trials. , 2007, Oncology.

[40]  Michael J. McGuire,et al.  A Peptide Selected by Biopanning Identifies the Integrin αvβ6 as a Prognostic Biomarker for Nonsmall Cell Lung Cancer , 2007 .

[41]  J. Manola,et al.  Blood-Based Biomarkers of SU11248 Activity and Clinical Outcome in Patients with Metastatic Imatinib-Resistant Gastrointestinal Stromal Tumor , 2007, Clinical Cancer Research.

[42]  Domenico Ribatti,et al.  The discovery of endothelial progenitor cells. An historical review. , 2007, Leukemia research.

[43]  D. Ribatti,et al.  A possible role of thymidine phosphorylase expression and5-fluorouracil increased sensitivity in oropharyngeal cancer patients , 2007, Journal of cellular and molecular medicine.

[44]  Jagat Narula,et al.  Molecular imaging in cardiology , 2007 .

[45]  K. Nicolay,et al.  Early in vivo assessment of angiostatic therapy efficacy by molecular MRI , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[46]  R. Stupp,et al.  Targeting brain-tumor stem cells , 2007, Nature Biotechnology.

[47]  A. Sinusas,et al.  Imaging angiogenesis. , 2007, Current opinion in biotechnology.

[48]  J. Roth,et al.  A peptide selected by biopanning identifies the integrin alphavbeta6 as a prognostic biomarker for nonsmall cell lung cancer. , 2007, Cancer research.

[49]  E. Crivellato,et al.  The history of the angiogenic switch concept , 2007, Leukemia.

[50]  I. Bayazitov,et al.  A perivascular niche for brain tumor stem cells. , 2007, Cancer cell.

[51]  G. Broggi,et al.  Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells , 2006, Nature.

[52]  G. Koren,et al.  A Pilot Pharmacokinetic and Antiangiogenic Biomarker Study of Celecoxib and Low-dose Metronomic Vinblastine or Cyclophosphamide in Pediatric Recurrent Solid Tumors , 2006, Journal of pediatric hematology/oncology.

[53]  Jennifer I. Hare,et al.  Pharmacokinetics and pharmacodynamics of lipidic nano-particles in cancer. , 2006, Anti-cancer agents in medicinal chemistry.

[54]  Chiara Brignole,et al.  Targeting liposomal chemotherapy via both tumor cell-specific and tumor vasculature-specific ligands potentiates therapeutic efficacy. , 2006, Cancer research.

[55]  W. Arap,et al.  Display technologies: Application for the discovery of drug and gene delivery agents , 2006, Advanced Drug Delivery Reviews.

[56]  J. Dick,et al.  Targeting of CD44 eradicates human acute myeloid leukemic stem cells , 2006, Nature Medicine.

[57]  Qiulian Wu,et al.  Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. , 2006, Cancer research.

[58]  Masatomo Kobayashi,et al.  Drosophila IKK-Related Kinase Regulates Nonapoptotic Function of Caspases via Degradation of IAPs , 2006, Cell.

[59]  A. Goldhirsch,et al.  Circulating endothelial-cell kinetics and viability predict survival in breast cancer patients receiving metronomic chemotherapy. , 2006, Blood.

[60]  D. Ribatti,et al.  Thymidine phosphorylase (platelet-derived endothelial cell growth factor) as a target for capecitabine: from biology to the bedside. , 2006, Recent patents on anti-cancer drug discovery.

[61]  W. Chan,et al.  Functional MR imaging of tumor angiogenesis predicts outcome of patients with acute myeloid leukemia , 2006, Leukemia.

[62]  B. Thürlimann,et al.  Circulating endothelial cells and angiogenic serum factors during neoadjuvant chemotherapy of primary breast cancer , 2006, British Journal of Cancer.

[63]  R. Figlin,et al.  Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[64]  R. Schiffelers,et al.  RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature. , 2005, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[65]  J. Lewin,et al.  Novel Phase I Dose De-escalation Design Trial to Determine the Biological Modulatory Dose of the Antiangiogenic Agent SU5416 , 2005, Clinical Cancer Research.

[66]  R. Galli,et al.  Tie2 identifies a hematopoietic monocytes required for tumor lineage of proangiogenic vessel formation and a mesenchymal population of pericyte progenitors , 2005 .

[67]  Luigi Naldini,et al.  Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. , 2005, Cancer cell.

[68]  Z. Werb,et al.  PDGFRβ+ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival , 2005, Nature Cell Biology.

[69]  S. Forman,et al.  Nonproliferating CML CD34+ progenitors are resistant to apoptosis induced by a wide range of proapoptotic stimuli , 2005, Leukemia.

[70]  Hong Zhang,et al.  Circulating endothelial progenitor cells in multiple myeloma: implications and significance. , 2005, Blood.

[71]  J. Wood,et al.  Soluble markers for the assessment of biological activity with PTK787/ZK 222584 (PTK/ZK), a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor in patients with advanced colorectal cancer from two phase I trials. , 2005, Annals of oncology : official journal of the European Society for Medical Oncology.

[72]  B. Druker,et al.  Oncogenes and Tumor Suppressors (795 articles) , 2004 .

[73]  A. Zito,et al.  Thymidine Phosphorylase Profiles in Nonmalignant and Malignant Pancreatic Tissue. Potential Therapeutic Role of Capecitabine on Tumoral and Endothelial Cells and Tumor-Infiltrating Macrophages , 2005, Immunopharmacology and immunotoxicology.

[74]  A. Klibanov,et al.  Ligand-carrying gas-filled microbubbles: ultrasound contrast agents for targeted molecular imaging. , 2005, Bioconjugate chemistry.

[75]  M. Reiser,et al.  Neovascularization of bone marrow in patients with diffuse multiple myeloma , 2004, Cancer.

[76]  D. Ribatti,et al.  Vascular endothelial growth factor concentrations in the plasma-activated platelets rich (P-APR) of healthy controls and colorectal cancer patients. , 2004, Oncology reports.

[77]  B. Fingleton,et al.  Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. , 2004, Cancer cell.

[78]  K. Alitalo,et al.  Adult bone marrow-derived cells recruited during angiogenesis comprise precursors for periendothelial vascular mural cells. , 2004, Blood.

[79]  Lin Zhang,et al.  Tumor-infiltrating dendritic cell precursors recruited by a β-defensin contribute to vasculogenesis under the influence of Vegf-A , 2004, Nature Medicine.

[80]  Arnon Nagler,et al.  CXCR4 regulates migration and development of human acute myelogenous leukemia stem cells in transplanted NOD/SCID mice. , 2004, Cancer research.

[81]  Pauline Chu,et al.  A novel antiangiogenesis therapy using an integrin antagonist or anti-Flk-1 antibody coated 90Y-labeled nanoparticles. , 2004, International journal of radiation oncology, biology, physics.

[82]  Pieter Wesseling,et al.  Aminopeptidase A is a functional target in angiogenic blood vessels. , 2004, Cancer cell.

[83]  Josefina Garcia.  Tumor-infiltrating dendritic cell precursors recruited by a beta-defensin contribute to vasculogenesis under the influence of Vegf-A , 2004 .

[84]  M. Carducci,et al.  Differentiation therapy. , 2020, Current opinion in pharmacology.

[85]  D. Ribatti,et al.  Vascular damage and anti-angiogenic effects of tumor vessel-targeted liposomal chemotherapy. , 2003, Cancer research.

[86]  R. Kerbel,et al.  Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells. , 2003, Cancer research.

[87]  R. Ohno,et al.  Treatment of acute promyelocytic leukemia: strategy toward further increase of cure rate , 2003, Leukemia.

[88]  J. Berkhof,et al.  Potential role of platelets in endothelial damage observed during treatment with cisplatin, gemcitabine, and the angiogenesis inhibitor SU5416. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[89]  Giovanni Martinelli,et al.  Continuous infusion of endostatin inhibits differentiation, mobilization, and clonogenic potential of endothelial cell progenitors. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[90]  L. Camacho.  Clinical applications of retinoids in cancer medicine. , 2003, Journal of biological regulators and homeostatic agents.

[91]  J. Folkman.  Role of angiogenesis in tumor growth and metastasis. , 2002, Seminars in oncology.

[92]  Theresa M Allen,et al.  Internalizing antibodies are necessary for improved therapeutic efficacy of antibody-targeted liposomal drugs. , 2002, Cancer research.

[93]  Giorgio Colombo,et al.  Structure-Activity Relationships of Linear and Cyclic Peptides Containing the NGR Tumor-homing Motif* , 2002, The Journal of Biological Chemistry.

[94]  Koichi Hattori,et al.  Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy? , 2002, Nature Reviews Cancer.

[95]  T. Allen.  Ligand-targeted therapeutics in anticancer therapy , 2002, Nature Reviews Cancer.

[96]  L. Ellis,et al.  Phase I study of recombinant human endostatin in patients with advanced solid tumors. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[97]  B. Seon.  Expression of endoglin (CD105) in tumor blood vessels , 2002, International journal of cancer.

[98]  J. Monson,et al.  Soluble FLT-1 is detectable in the sera of colorectal and breast cancer patients. , 2002, Anticancer research.

[99]  Wadih Arap,et al.  Differential binding of drugs containing the NGR motif to CD13 isoforms in tumor vessels, epithelia, and myeloid cells. , 2002, Cancer research.

[100]  R. Brekken,et al.  Vascular endothelial growth factor and vascular targeting of solid tumors. , 2001, Anticancer research.

[101]  Rakesh K. Jain,et al.  Normalizing tumor vasculature with anti-angiogenic therapy: A new paradigm for combination therapy , 2001, Nature Medicine.

[102]  G. Pruneri,et al.  Kinetics and viability of circulating endothelial cells as surrogate angiogenesis marker in an animal model of human lymphoma. , 2001, Cancer research.

[103]  A. Goldhirsch,et al.  Resting and activated endothelial cells are increased in the peripheral blood of cancer patients. , 2001, Blood.

[104]  D. Taatjes,et al.  Nuclear targeting and retention of anthracycline antitumor drugs in sensitive and resistant tumor cells. , 2001, Current medicinal chemistry.

[105]  H. Kosmehl,et al.  Targeted delivery of tissue factor to the ED-B domain of fibronectin, a marker of angiogenesis, mediates the infarction of solid tumors in mice. , 2001, Cancer research.

[106]  A. Blann,et al.  Serum soluble vascular cell adhesion molecule-1: role as a surrogate marker of angiogenesis. , 2000, Journal of the National Cancer Institute.

[107]  S. Baruchel,et al.  Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. , 2000, The Journal of clinical investigation.

[108]  John Calvin Reed,et al.  Expression of Bcl-2-related genes in normal and AML progenitors: changes induced by chemotherapy and retinoic acid , 1999, Leukemia.

[109]  V. Reuter,et al.  Prostate-specific membrane antigen is produced in tumor-associated neovasculature. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[110]  P. Meltzer,et al.  Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. , 1999, The American journal of pathology.

[111]  G. Yancopoulos,et al.  Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. , 1999, Science.

[112]  R. Jain.  The next frontier of molecular medicine: Delivery of therapeutics , 1998, Nature Medicine.

[113]  E. Ruoslahti,et al.  Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. , 1998, Science.

[114]  J. Folkman,et al.  Successful treatment of infantile hemangiomas with interferon-α-2b , 1997 .

[115]  C. Hellerqvist,et al.  Phase I study of the antineovascularization drug CM101. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[116]  J. Folkman,et al.  Successful treatment of infantile hemangiomas with interferon-alpha-2b. , 1997, Journal of pediatric hematology/oncology.

[117]  P. Wesseling,et al.  AMINOPEPTIDASE A IS A CONSTITUENT OF ACTIVATED PERICYTES IN ANGIOGENESIS , 1996, The Journal of pathology.

[118]  Erkki Ruoslahti,et al.  Organ targeting In vivo using phage display peptide libraries , 1996, Nature.

[119]  A. Gazdar,et al.  Up-regulation of endoglin on vascular endothelial cells in human solid tumors: implications for diagnosis and therapy. , 1995, Clinical cancer research : an official journal of the American Association for Cancer Research.

[120]  D. Cheresh,et al.  Requirement of vascular integrin alpha v beta 3 for angiogenesis. , 1994, Science.

[121]  T. Tsuruo,et al.  Role of aminopeptidase N (CD13) in tumor‐cell invasion and extracellular matrix degradation , 1993, International journal of cancer.

[122]  V. Gerkis,et al.  Variable O-glycosylation of CD13 (aminopeptidase N). , 1991, The Journal of biological chemistry.