Gene therapy strategies developed to interfere with the normal function of vascular endothelial growth factor receptors have been successfully used in different experimental models to block tumor angiogenesis and to inhibit tumor growth. Many of the first clinical protocols for cancer gene therapy involved the ex vivo modification of freshly isolated tumor cells with cytokines. New antiangiogenic drugs will probably be used in combination with existing drugs but perhaps also used alone as longterm maintenance therapy. Purpose antiangiogenic therapy inhibits the growth of new blood vessels. Nov, 2000 based on their own antiangiogenic gene therapy research, the authors evaluated the published experience with antiangiogenic gene therapy models using the national library of medicines pubmed search service and the reference lists of the publications cited. Endothelial cells represent attractive targets for therapy, because tumor expansion depends on angiogenesis and endothelial cells are less likely to develop drug resistance than the tumor cells that surround them 11,22. Because of its importance, vegf has been at the center stage of antiangiogenic therapy. Gene therapy angiogenesis inhibitor antiangiogenic therapy endothelial precursor cell angiogenic inhibitor these keywords were added by machine and not by the authors. Current status of gene therapy for lung cancer and head and. Hepatocellular carcinoma hcc is a hypervascular cancer, and antiangiogenic gene therapy might be suitable for hcc. Benckendorff, 1andreas holmgaard, jacob giehm mikkelsen. Based on their own antiangiogenic gene therapy research, the authors evaluated the published experience with antiangiogenic gene therapy models using the national library of medicines pubmed. Antiangiogenic therapy definition of antiangiogenic therapy.
Gene therapy represents a possible alternative to the chronic delivery of recombinant antiangiogenic proteins to cancer patients. Gene electrotransfer is based on electroporation, a physical method, which causes a transient increase in cell membrane permeability due to the application of electric pulses and thus enables the transport of. Vegf therapy, and, if the tumor is kras wildtype, antiepidermal growth factor receptor egfr therapy. Based on the observation that solid tumor growth is angiogenic dependent, and gliomas are among the most angiogenic of all tumors, therapeutic strategies aimed at inhibiting angiogenesis are theoretically attractive. Now, several years after fda approval of an antivegf antibody as the first antiangiogenic agent, many patients with cancer and ocular neovascularization have benefited from vegftargeted therapy. Gene therapy represents an attractive alternative to recombinant protein. Adenoassociated virus 2mediated antiangiogenic cancer gene. Antiangiogenic gene therapy in a rat glioma model using a. Angiogenic and antiangiogenic gene therapy is a new therapeutic approach to the treatment of. Jul 28, 2015 most of all, this success has been facilitated because of 1 the fact that the eye is an effortlessly accessible, exceedingly compartmentalized, and immuneprivileged organ offering a unique advantage as a gene therapy target, and 2 significant progress toward efficient, sustained transduction of cells within the retina having been achieved. Future prospects and challenges of antiangiogenic cancer. Definition antiangiogenesis therapy is one of two types of drugs in a new class of medicines that restores health by controlling blood vessel growth. Antiangiogenesis gene therapy and angiogenesis inhibitors anti angiogenic gene therapy targeting endothelial cells ecs for the majority of cancer therapy strategies, the tumor vasculature has provided issues for drug delivery, as it is a barrier that prevents drugs from reaching tumor cells. Gene therapy strategies that result in constitutive expression of an antiangiogenic protein would be expected to be more effective in this setting than a gene therapy approach targeting a tumor cell that might quickly develop an escape mechanism.
Antiangiogenic eye gene therapy human gene therapy. Antiangiogenic gene therapy of cancer utilizing a recombinant. Progress in antiangiogenic gene therapy of cancer feldman. Pdf antiangiogenic approaches for cancer gene therapy.
One of the most recent and exciting approaches in cancer gene therapy is the ability to target the developing blood supply of the tumor. An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels angiogenesis. Antiangiogenic gene therapy for hepatocellular carcinoma. Angiogenic and antiangiogenic gene therapy gene therapy. Antiangiogenic agents have recently received much widespread attention but strategies for their optimal use are still being developed. The application of an antiangiogenic gene thrombospondin1 in the treatment of human prostate cancer xenografts. The other medication is called proangiogenic therapy. Original article suppression of choroidal neovascularization by aavbased dualacting antiangiogenic gene therapy anne louise askou, 1sidsel alsing, josephine n. Based on their own antiangiogenic gene therapy research, the authors evaluated the published experience with antiangiogenic gene therapy models using the. Angiogenesis inhibitors are unique cancerfighting agents because they block the growth of blood vessels that support tumor growth rather than blocking the growth of tumor cells themselves. Antiangiogenic therapy is a potentially attractive approach to cancer treatment, in that many key targets are expressed on genetically stable vascular endothelial cells, and the approach offers the potential for treating a broad range of solid tumors. Angiogenesis inhibitors interfere in several ways with various steps in blood vessel growth.
Some angiogenesis inhibitors are endogenous and a normal part of the bodys control and others are obtained exogenously through pharmaceutical drugs or diet. Antiangiogenic gene therapy in cancer bentham science. Antiangiogenic therapy an overview sciencedirect topics. This process is experimental and the keywords may be updated as the learning algorithm improves. Antiangiogenic agents in neoadjuvant therapy lisa a. Oct 18, 2005 angiogenic and antiangiogenic gene therapy is a new therapeutic approach to the treatment of cardiovascular and cancer patients, respectively. In the presence of the appropriate in vivo control, however, it became apparent that in many cases, cytokine modification may be little better than more conventional adjuvantbased cancer cell therapies with no gene transfer component. Modified genes are not passed on from one generation to the next. Antiangiogenic gene therapy yihai cao laboratory of angiogenesis research, microbiology and tumor biology center, karolinska institute, s171 77 stockholm, sweden received 8 november 1999 abstract a number of potent endogenous inhibitors targeting the tumor vasculature have recently been identi ed in tumor. Jul 04, 2001 gene therapy represents an interesting alternative for the effective delivery of antiangiogenic therapy, and a number of studies 916 have demonstrated that a gene therapybased antiangiogenesis approach is an effective means of reducing tumor growth in animal models. At present, monoclonal antibodies and smallmolecule. A novel antiangiogenic gene therapy, added to another antiangiogenic agent, avastin bevacizumab, led to significantly better overall survival os in recurrent glioblastoma multiforme gbm compared with historical patients treated with avastin alone, a small phase 2 trial showed. Carey, md university of north carolina lineberger comprehensive cancer center.
With the role of angiogenesis in tumor growth and progression firmly established, considerable effort has been directed to antiangiogenic therapy as a new modality to treat human cancers. Antiangiogenic gene therapy, added to standard treatment. Update on antiangiogenic therapy for metastatic colorectal cancer. Polyethylene glycolpolyllysine block copolymers pegplys with thiol groups in the side chain of the plys segment were synthesized and applied for preparation of disulfide crosslinked polyplex micelles through ion complexation with plasmid. Peg conjugated vegf sirna for antiangiogenic gene therapy. A read is counted each time someone views a publication summary such as the title, abstract, and list of authors, clicks on a figure, or views or downloads the fulltext. Treatment algorithms must be updated to accommodate all three agents as potential therapy for patients with mcrc. Gene therapy with plasmid amep antiangiogenic metargidin peptide has recently been studied as a potential targeted therapy for melanoma.
Inducing normal host tissues to produce high circulating levels of these proteins may be more effective than targeting antiangiogenic genes to tumor tissue specifically. Ideally, gene therapy approaches for delivery of antiangiogenic agents would convert the body into its own factory for producing these proteins 18, 39. Angiogenic and antiangiogenic gene therapy is a new therapeutic approach to the treatment of cardiovascular and cancer patients, respectively. Antiangiogenic gene therapy of myeloproliferative disease. Dec 23, 2004 antiangiogenic gene therapy offers an attractive approach to the treatment of a variety of malignancies, including those of the hematological system. An appealing feature of antiangiogenic gene therapy is that the tumor vasculature is a readily accessible target, particularly when the carrier and its gene are administered systemically. Pdf antiangiogenic gene therapy with soluble vegfreceptors. Viral vectortargeted antiangiogenic gene therapy utilizing. Despite recent advances in neurosurgery, radiation, and chemotherapy, the prognosis of patients with malignant gliomas remains dismal.
Antiangiogenic gene therapy, gene therapy and regulation. Antiangiogenic gene therapy with soluble vegfreceptors 1, 2 and 3 together with paclitaxel prolongs survival of mice with human ovarian carcinoma. Inhibition of tumor angiogenesis using antiangiogenic drugs and gene transfer approaches has suggested the potential of this form of therapy in controlling tumor growth. In this manner, direct infection of the tumor cell would not be required, as opposed to gene therapy to restore defective copies of a tumor suppressor such as p53. In this study, a polyplex micelle was developed as a potential formulation for antiangiogenic gene therapy of subcutaneous pancreatic tumor model. Greater than 40 endogenous inhibitors of angiogenesis have been characterized.
Antiangiogenic gene therapy of solid tumor by systemic. Antiangiogenic gene therapy of cancer springerlink. These studies also show antiangiogenic agents are more effective against small than large tumours, so early application in adjuvant therapy may be their future role. Antiangiogenic agents have recently received much widespread.
Sep 23, 2016 targeting of angiogenesis activators or the delivery of inhibitors by gene electrotransfer is a promising approach for cancer therapy. Suppression of choroidal neovascularization by aavbased dual. In addition to the three antiangiogenic agents that have already gained approval by the fda, numerous other agents with varying. Recent studies have reported that antiangiogenic gene delivery into cancer cells inhibits growth of certain tumors in vivo. This study is the first attempt to test the multigenic system in aav vectors, and the provided data suggest that dualacting antiangiogenic gene therapy based on multigenic aav vectors is an important therapeutic tool in future eye gene therapy for cnvrelated diseases. Antiangiogenic gene therapy, cancer, genes, vascular endothelial growth factor vegf, receptor, angiogenesis, antiangiogenesis, angiopoietins, tie receptor, fibroblast growth factor. The effects of current gene therapy approaches are limited to the treated patients cells.
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