The impact of tumor microenvironment on cancer treatment and its modulation by direct and indirect antivascular strategies
Tumor cells exploit their microenvironment by growth factors and cytokines such as vascular endothelial growth factor (VEGF) to stimulate abnormal vessel formation that is leaky and tortuous, causing irregular blood flow. The combination of poor perfusion, raised interstitial fluid pressure and area...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
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2012
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| _version_ | 1797086757122998272 |
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| author | Fokas, E Mckenna, W Muschel, R |
| author_facet | Fokas, E Mckenna, W Muschel, R |
| author_sort | Fokas, E |
| collection | OXFORD |
| description | Tumor cells exploit their microenvironment by growth factors and cytokines such as vascular endothelial growth factor (VEGF) to stimulate abnormal vessel formation that is leaky and tortuous, causing irregular blood flow. The combination of poor perfusion, raised interstitial fluid pressure and areas of vascular collapse leads to hypoxia within tumor. The latter activates factors such as hypoxia inducible factor 1 (HIF-1) that serve to make cancer cells more aggressive and also markedly influences the response of malignant tumors to conventional irradiation and chemotherapy. Accumulating data now suggest that blockade of oncogenic signaling, for example by PI3K/Akt/mTOR inhibitors, might consist a promising strategy since these agents do not only possess antitumor effects but can also alter tumor vasculature and oxygenation to improve the response to radiation and chemotherapy. In many cases, these changes are related to downregulation of HIF-1α and VEGF. Here, we review the pathophysiology of tumor microenvironment (TME) and how it adversely affects cancer treatment. The complex interaction of tumor vasculature and radiotherapy is examined together the preclinical evidence supporting a proinvasive/metastatic role for ionising radiation. We will discuss the expanding role of oncogenic signaling, especially PI3K/Akt/mTOR, on tumor angiogenesis. Special emphasis will be paid to the potential of different oncogenic pathways blockade and other indirect antivascular strategies to alter the TME for the benefit of cancer treatment, as an alternative to the classical angiogenetic treatment. © 2012 Springer Science+Business Media, LLC. |
| first_indexed | 2024-03-07T02:26:32Z |
| format | Journal article |
| id | oxford-uuid:a5cb2903-54b6-4dd4-83bc-aef058fd8854 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:26:32Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:a5cb2903-54b6-4dd4-83bc-aef058fd88542022-03-27T02:42:55ZThe impact of tumor microenvironment on cancer treatment and its modulation by direct and indirect antivascular strategiesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a5cb2903-54b6-4dd4-83bc-aef058fd8854EnglishSymplectic Elements at Oxford2012Fokas, EMckenna, WMuschel, RTumor cells exploit their microenvironment by growth factors and cytokines such as vascular endothelial growth factor (VEGF) to stimulate abnormal vessel formation that is leaky and tortuous, causing irregular blood flow. The combination of poor perfusion, raised interstitial fluid pressure and areas of vascular collapse leads to hypoxia within tumor. The latter activates factors such as hypoxia inducible factor 1 (HIF-1) that serve to make cancer cells more aggressive and also markedly influences the response of malignant tumors to conventional irradiation and chemotherapy. Accumulating data now suggest that blockade of oncogenic signaling, for example by PI3K/Akt/mTOR inhibitors, might consist a promising strategy since these agents do not only possess antitumor effects but can also alter tumor vasculature and oxygenation to improve the response to radiation and chemotherapy. In many cases, these changes are related to downregulation of HIF-1α and VEGF. Here, we review the pathophysiology of tumor microenvironment (TME) and how it adversely affects cancer treatment. The complex interaction of tumor vasculature and radiotherapy is examined together the preclinical evidence supporting a proinvasive/metastatic role for ionising radiation. We will discuss the expanding role of oncogenic signaling, especially PI3K/Akt/mTOR, on tumor angiogenesis. Special emphasis will be paid to the potential of different oncogenic pathways blockade and other indirect antivascular strategies to alter the TME for the benefit of cancer treatment, as an alternative to the classical angiogenetic treatment. © 2012 Springer Science+Business Media, LLC. |
| spellingShingle | Fokas, E Mckenna, W Muschel, R The impact of tumor microenvironment on cancer treatment and its modulation by direct and indirect antivascular strategies |
| title | The impact of tumor microenvironment on cancer treatment and its modulation by direct and indirect antivascular strategies |
| title_full | The impact of tumor microenvironment on cancer treatment and its modulation by direct and indirect antivascular strategies |
| title_fullStr | The impact of tumor microenvironment on cancer treatment and its modulation by direct and indirect antivascular strategies |
| title_full_unstemmed | The impact of tumor microenvironment on cancer treatment and its modulation by direct and indirect antivascular strategies |
| title_short | The impact of tumor microenvironment on cancer treatment and its modulation by direct and indirect antivascular strategies |
| title_sort | impact of tumor microenvironment on cancer treatment and its modulation by direct and indirect antivascular strategies |
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