Optimizing the Delivery of Cancer Drugs That Block Angiogenesis

Optimal delivery systems for antiangiogenic drugs must be developed to maximize clinical benefits and minimize adverse effects in cancer patients. Drugs that block angiogenesis are important components of first-line therapies for a number of human cancers. However, some of these agents have undesirable effects on the patient. Optimal delivery systems must be developed to maximize clinical benefits and minimize adverse effects in cancer patients. In this Perspective, we discuss these drug-related issues and propose ways to optimize antiangiogenic therapy by the development of new drug delivery systems.

[1]  D. Ingber,et al.  Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth , 1990, Nature.

[2]  Tracy T Batchelor,et al.  AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. , 2007, Cancer cell.

[3]  Robert Langer,et al.  Advancing the field of drug delivery: taking aim at cancer. , 2003, Cancer cell.

[4]  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.

[5]  Ricky T. Tong,et al.  Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer , 2004, Nature Medicine.

[6]  Dushyant V. Sahani,et al.  Biomarkers of response and resistance to antiangiogenic therapy , 2009, Nature Reviews Clinical Oncology.

[7]  Ma Dong,et al.  Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer , 2006 .

[8]  Yihai Cao,et al.  Improvement of antiangiogenic cancer therapy by understanding the mechanisms of angiogenic factor interplay and drug resistance. , 2009, Seminars in cancer biology.

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

[10]  Masahiro Inoue,et al.  Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. , 2009, Cancer cell.

[11]  Lars Holmgren,et al.  Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a lewis lung carcinoma , 1994, Cell.

[12]  Elena Bogdanovic,et al.  Vascular endothelial growth factor-mediated decrease in plasma soluble vascular endothelial growth factor receptor-2 levels as a surrogate biomarker for tumor growth. , 2008, Cancer research.

[13]  Robert Langer,et al.  Multi-pulse drug delivery from a resorbable polymeric microchip device , 2003, Nature materials.

[14]  J. Folkman.  Tumor angiogenesis: therapeutic implications. , 1971, The New England journal of medicine.

[15]  A. Hansen,et al.  Anti-VEGF agents confer survival advantages to tumor-bearing mice by improving cancer-associated systemic syndrome , 2008, Proceedings of the National Academy of Sciences.

[16]  J. Davies,et al.  Targeting angiogenesis with a conjugate of HPMA copolymer and TNP-470 , 2004, Nature Medicine.

[17]  Vladimir P Torchilin,et al.  Cationic charge determines the distribution of liposomes between the vascular and extravascular compartments of tumors. , 2002, Cancer research.

[18]  Gabriele Bergers,et al.  Modes of resistance to anti-angiogenic therapy , 2008, Nature Reviews Cancer.

[19]  R. Langer,et al.  Drug delivery and targeting. , 1998, Nature.

[20]  R. Jain.  Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy , 2005, Science.

[21]  J. Berlin,et al.  Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. , 2004, The New England journal of medicine.

[22]  D. McDonald,et al.  Rapid vascular regrowth in tumors after reversal of VEGF inhibition. , 2006, The Journal of clinical investigation.

[23]  A. Goldhirsch,et al.  Metronomic cyclophosphamide and capecitabine combined with bevacizumab in advanced breast cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  John T Santini,et al.  Chronic, programmed polypeptide delivery from an implanted, multireservoir microchip device , 2006, Nature Biotechnology.

[25]  John M L Ebos,et al.  Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. , 2009, Cancer cell.

[26]  D. Gewirtz,et al.  Sustained enhancement of liposome-mediated gene delivery and gene expression in human breast tumour cells by ionizing radiation. , 1999, International journal of radiation biology.

[27]  R. Kerbel,et al.  Molecular and cellular biomarkers for angiogenesis in clinical oncology. , 2007, Drug discovery today.

[28]  R. Kerbel,et al.  Improving conventional or low dose metronomic chemotherapy with targeted antiangiogenic drugs. , 2007, Cancer research and treatment : official journal of Korean Cancer Association.

[29]  Gabriele Bergers,et al.  Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice. , 2000, The Journal of clinical investigation.

[30]  R K Gupta,et al.  Pulsed controlled-released system for potential use in vaccine delivery. , 1996, Journal of pharmaceutical sciences.

[31]  D. M. Lynn,et al.  Controlling interlayer diffusion to achieve sustained, multiagent delivery from layer-by-layer thin films , 2006, Proceedings of the National Academy of Sciences.

[32]  D. McDonald,et al.  Mechanisms of adverse effects of anti-VEGF therapy for cancer , 2007, British Journal of Cancer.

[33]  Sonja Loges,et al.  Silencing or fueling metastasis with VEGF inhibitors: antiangiogenesis revisited. , 2009, Cancer cell.

[34]  R. Langer,et al.  Enzymatically activated microencapsulated liposomes can provide pulsatile drug release , 1990, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[35]  D. Yamashiro,et al.  VEGF blocking therapy in the treatment of cancer , 2003, Expert opinion on biological therapy.

[36]  Michael I Dorrell,et al.  Combination angiostatic therapy completely inhibits ocular and tumor angiogenesis , 2007, Proceedings of the National Academy of Sciences.

[37]  Oriol Casanovas,et al.  Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. , 2005, Cancer cell.

[38]  J. Folkman,et al.  Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. , 2000, Cancer research.

[39]  J. Folkman.  Angiogenesis: an organizing principle for drug discovery? , 2007, Nature reviews. Drug discovery.

[40]  Philippe Leboulch,et al.  Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2 , 2003, Nature Medicine.

[41]  G. Demetri,et al.  Molecular basis for sunitinib efficacy and future clinical development , 2007, Nature Reviews Drug Discovery.

[42]  T. Libermann,et al.  Soluble endoglin contributes to the pathogenesis of preeclampsia , 2006, Nature Medicine.

[43]  J. Christensen,et al.  Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy , 2007, Proceedings of the National Academy of Sciences.

[44]  Yihai Cao,et al.  Angiogenic factors FGF2 and PDGF-BB synergistically promote murine tumor neovascularization and metastasis. , 2007, The Journal of clinical investigation.

[45]  Rakesh K. Jain,et al.  Vascular Normalization by Vascular Endothelial Growth Factor Receptor 2 Blockade Induces a Pressure Gradient Across the Vasculature and Improves Drug Penetration in Tumors , 2004, Cancer Research.

[46]  Lei Xu,et al.  Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. , 2004, Cancer cell.

[47]  M. Cima,et al.  A controlled-release microchip , 1999, Nature.

[48]  R. Langer,et al.  Isolations of a cartilage factor that inhibits tumor neovascularization. , 1976, Science.