Trends and Challenges in Tumor Anti-Angiogenic Therapies
Excessive abnormal angiogenesis plays a pivotal role in tumor progression and is a hallmark of solid tumors. This process is driven by an imbalance between pro- and anti-angiogenic factors dominated by the tissue hypoxia-triggered overproduction of vascular endothelial growth factor (VEGF). VEGF-med...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/9/1102 |
| _version_ | 1797710317222887424 |
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| author | József Jászai Mirko H.H. Schmidt |
| author_facet | József Jászai Mirko H.H. Schmidt |
| author_sort | József Jászai |
| collection | DOAJ |
| description | Excessive abnormal angiogenesis plays a pivotal role in tumor progression and is a hallmark of solid tumors. This process is driven by an imbalance between pro- and anti-angiogenic factors dominated by the tissue hypoxia-triggered overproduction of vascular endothelial growth factor (VEGF). VEGF-mediated signaling has quickly become one of the most promising anti-angiogenic therapeutic targets in oncology. Nevertheless, the clinical efficacy of this approach is severely limited in certain tumor types or shows only transient efficacy in patients. Acquired or intrinsic therapy resistance associated with anti-VEGF monotherapeutic approaches indicates the necessity of a paradigm change when targeting neoangiogenesis in solid tumors. In this context, the elaboration of the conceptual framework of “vessel normalization” might be a promising approach to increase the efficacy of anti-angiogenic therapies and the survival rates of patients. Indeed, the promotion of vessel maturation instead of regressing tumors by vaso-obliteration could result in reduced tumor hypoxia and improved drug delivery. The implementation of such anti-angiogenic strategies, however, faces several pitfalls due to the potential involvement of multiple pro-angiogenic factors and modulatory effects of the innate and adaptive immune system. Thus, effective treatments bypassing relapses associated with anti-VEGF monotherapies or breaking the intrinsic therapy resistance of solid tumors might use combination therapies or agents with a multimodal mode of action. This review enumerates some of the current approaches and possible future directions of treating solid tumors by targeting neovascularization. |
| first_indexed | 2024-03-12T06:50:26Z |
| format | Article |
| id | doaj.art-b014a9c0880e4f1fa4ad6d7f128470b6 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T06:50:26Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj.art-b014a9c0880e4f1fa4ad6d7f128470b62023-09-03T00:20:33ZengMDPI AGCells2073-44092019-09-0189110210.3390/cells8091102cells8091102Trends and Challenges in Tumor Anti-Angiogenic TherapiesJózsef Jászai0Mirko H.H. Schmidt1Institute of Anatomy, Medical Faculty Carl Gustav Carus, Technische Universität Dresden School of Medicine, 01307 Dresden, GermanyInstitute of Anatomy, Medical Faculty Carl Gustav Carus, Technische Universität Dresden School of Medicine, 01307 Dresden, GermanyExcessive abnormal angiogenesis plays a pivotal role in tumor progression and is a hallmark of solid tumors. This process is driven by an imbalance between pro- and anti-angiogenic factors dominated by the tissue hypoxia-triggered overproduction of vascular endothelial growth factor (VEGF). VEGF-mediated signaling has quickly become one of the most promising anti-angiogenic therapeutic targets in oncology. Nevertheless, the clinical efficacy of this approach is severely limited in certain tumor types or shows only transient efficacy in patients. Acquired or intrinsic therapy resistance associated with anti-VEGF monotherapeutic approaches indicates the necessity of a paradigm change when targeting neoangiogenesis in solid tumors. In this context, the elaboration of the conceptual framework of “vessel normalization” might be a promising approach to increase the efficacy of anti-angiogenic therapies and the survival rates of patients. Indeed, the promotion of vessel maturation instead of regressing tumors by vaso-obliteration could result in reduced tumor hypoxia and improved drug delivery. The implementation of such anti-angiogenic strategies, however, faces several pitfalls due to the potential involvement of multiple pro-angiogenic factors and modulatory effects of the innate and adaptive immune system. Thus, effective treatments bypassing relapses associated with anti-VEGF monotherapies or breaking the intrinsic therapy resistance of solid tumors might use combination therapies or agents with a multimodal mode of action. This review enumerates some of the current approaches and possible future directions of treating solid tumors by targeting neovascularization.https://www.mdpi.com/2073-4409/8/9/1102anti-angiogenesis therapy of cancersprouting angiogenesisstromal microenviromentevasive resistancevessel normalizationanti-VEGF therapyBevacizumabAfliberceptsmall-molecule multikinase-inhibitorsangiogenesis inhibitors |
| spellingShingle | József Jászai Mirko H.H. Schmidt Trends and Challenges in Tumor Anti-Angiogenic Therapies Cells anti-angiogenesis therapy of cancer sprouting angiogenesis stromal microenviroment evasive resistance vessel normalization anti-VEGF therapy Bevacizumab Aflibercept small-molecule multikinase-inhibitors angiogenesis inhibitors |
| title | Trends and Challenges in Tumor Anti-Angiogenic Therapies |
| title_full | Trends and Challenges in Tumor Anti-Angiogenic Therapies |
| title_fullStr | Trends and Challenges in Tumor Anti-Angiogenic Therapies |
| title_full_unstemmed | Trends and Challenges in Tumor Anti-Angiogenic Therapies |
| title_short | Trends and Challenges in Tumor Anti-Angiogenic Therapies |
| title_sort | trends and challenges in tumor anti angiogenic therapies |
| topic | anti-angiogenesis therapy of cancer sprouting angiogenesis stromal microenviroment evasive resistance vessel normalization anti-VEGF therapy Bevacizumab Aflibercept small-molecule multikinase-inhibitors angiogenesis inhibitors |
| url | https://www.mdpi.com/2073-4409/8/9/1102 |
| work_keys_str_mv | AT jozsefjaszai trendsandchallengesintumorantiangiogenictherapies AT mirkohhschmidt trendsandchallengesintumorantiangiogenictherapies |