Antiangiogenesis: Current Clinical Data and Future Perspectives

Drevs, Joachim; Laus, C.; Medinger, Michael; Schmidt-Gersbach, C.; Unger, Clemens

doi:10.1159/000068622

Cited by 28 publications

(13 citation statements)

References 22 publications

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“…[6][7][8] Here, these anti-angiogenic inhibitors are collectively reviewed and their anti-angiogenic effect and subsequent anti-tumor effect estimated. Then, a novel cancer chemotherapy targeting the angiogenic vasculature, anti-neovascular therapy (ANET), is discussed which uses traditional anti-cancer agents or photosensitizer.…”

Section: Introductionmentioning

confidence: 99%

Cancer Anti-angiogenic Therapy

Shimizu

Oku

2004

Biological & Pharmaceutical Bulletin

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Tumor angiogenesis affords new targets for cancer therapy, since inhibition of angiogenesis suppresses tumor growth by cutting out the supply of oxygen and nutrients. Anti-angiogenic therapy is thought to be free of the severe side effects that are usually seen with cytotoxic anticancer drugs. Furthermore, anti-angiogenic therapy is thought not only to eradicate primary tumor tissues, but also to suppress tumor metastases. However, it is uncertain whether this therapy causes tumor regression because it inhibits only angiogenic events. Recently, a novel anti-angiogenic therapy called anti-neovascular therapy (ANET) has become notable. This therapy inflicts indirect lethal damage on tumor cells by damaging newly formed blood vessels using anti-cancer drugs targeting the angiogenic vasculature, since cytotoxic anti-cancer drugs cause damage to proliferating neovascular endothelial cells as well as tumor cells. Moreover, neovascular endothelial cells would not be expected to acquire drug-resistance. Traditional chemotherapy, which directly targets tumor cells, has potential problems such as low specificity and severe side effects. On the contrary, in ANET, severe side effects may be suppressed, since traditional anti-cancer agents are delivered to the neovessels by DDS technology. Besides the usage of DDS technology, antineovascular scheduling of chemotherapy, or metronomic-dosing chemotherapy, has also been attempted in which anti-cancer drugs are administered on a schedule to damage neovessels. In this review, we describe traditional anti-angiogenic therapy and ANET. We also discuss anti-angiogenic cancer photodynamic therapy (PDT), since PDT is clinically applied to treat age-related macular degeneration (AMD), in which uncontrolled angiogenesis occurs.

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Section: Introductionmentioning

confidence: 99%

Cancer Anti-angiogenic Therapy

Shimizu

Oku

2004

Biological & Pharmaceutical Bulletin

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“…[11][12][13][14] Compared with protein therapy, there are several potential advantages. As a prelude to the potential clinical application of RI gene therapy, we cloned the human ri gene and inserted it in a retroviral vector pLNCX.…”

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confidence: 99%

Anti-tumor effect of hematopoietic cells carrying the gene of ribonuclease inhibitor

Chen

Tian

et al. 2004

Cancer Gene Ther

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Human ribonuclease inhibitor (hRI) is an acid protein with a molecular weight of 50 kDa. It can inhibit the activity of pancreatic RNase (RNase A). Angiogenin (Ang) is a member of the ribonuclease super family. It has 35% identity with RNase A and contains ribonucleolytic activity. The substrate specificity of angiogenin seems, however, to be more restricted than that of the pancreatic RNase. Since Ang is an important angiogenic factor and RI is a highly efficient inhibitor of Ang, it can be hypothesized that RI may be a latent antiangiogenic drug. This study focuses on the feasibility of transfecting the ri gene into mice hematopoietic cells and inducing the expression of the ri gene to block the angiogenesis of solid tumors. First, the cDNA gene of the ri from human placenta was cloned and inserted in a retroviral vector, pLNCX. The combined vector pLNCX-ri was transfected into retroviral packaging cells, PA317, and a clone producing a high titer of virus was obtained. Next, isolated hematopoietic cells from mice bone marrow were infected with viruses carrying the pLNCX-ri. The infected cells were then injected into lethally irradiated mice. The expression and the contribution of RI were assayed in vivo. After administration of hematopoietic cells carrying the ri gene, mice were implanted with B16 melanomas for 21 days. The results showed that tumors of control groups became large and well vascularized. In contrast, tumors from mice groups treated with hematopoietic cells carrying the ri gene were small and possessed a relatively low density of blood vessels. The inhibited growth rate of the tumors was 47%. This study demonstrated the potential utility of gene therapy for systemic delivery of a novel antiangiogenic agent -hRI.

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“…To date, no clear correlation has emerged between circulating and receptor bound levels of VEGF and other angiogenic factors. A large number of studies have demonstrated a strong association between elevated expression of VEGF by primary tumors and advanced disease or poor prognosis (including lymph node metastasis) in a variety of cancers [18,[29][30][31]. Protein and mRNA have been measured in tumor samples, and protein has also been measured in the circulation.…”

Section: Angiogenic Growth Factors and Their Receptorsmentioning

confidence: 99%

Circulating and imaging markers for angiogenesis

Pathak

Hochfeld

et al. 2008

Angiogenesis

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Abundant preclinical and indirect clinical data have for several decades convincingly supported the notion that anti-angiogenesis is an effective strategy for the inhibition of tumor growth. The recent success achieved in patients with metastatic colon carcinoma using a neutralizing antibody directed against vascular endothelial growth factor (VEGF) has translated preclinical optimism into a clinical reality.With this transformation in the field of angiogenesis has come a need for reliable surrogate markers. A surrogate marker by definition serves as a substitute for the underlying process in question, and in the case of angiogenesis, microvessel density (usually in so-called "hot-spots") has until now been the most widely used parameter. However, this parameter is more akin to a static "snapshot" and does not lend itself either to the dynamic in situ assessment of the status of the tumor microvasculature or to the molecular factors that regulate its growth and involution. This has led to an acute need for developing circulating and imaging markers of angiogenesis that can be monitored in vivo at repeated intervals in large number of patients with a variety of tumors in a non-invasive manner. Such markers of angiogenesis are the subject of this review.

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Antiangiogenesis: Current Clinical Data and Future Perspectives

Cited by 28 publications

References 22 publications

Cancer Anti-angiogenic Therapy

Cancer Anti-angiogenic Therapy

Anti-tumor effect of hematopoietic cells carrying the gene of ribonuclease inhibitor

Circulating and imaging markers for angiogenesis

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