Ways to improve tumor uptake and penetration of drugs into solid tumors
The main scope of this topic is to give an update on pharmacologic and non-pharmacologic approaches to enhance uptake and penetration of cancer drugs into tumors. Inadequate accumulation of drugs in tumors has emerged over the last decade as one of the main problems underlying therapeutic failure an...
में बचाया:
| मुख्य लेखकों: | , , |
|---|---|
| स्वरूप: | Online |
| भाषा: | अंग्रेज़ी |
| प्रकाशित: |
Frontiers Media SA
2021
|
| विषय: | |
| ऑनलाइन पहुंच: | 18680 |
| टैग: |
कोई टैग नहीं, इस रिकॉर्ड को टैग करने वाले पहले व्यक्ति बनें!
|
| _version_ | 1869530851254992896 |
|---|---|
| author | Ronald Berenson Angelo Corti Fabrizio Marcucci |
| author_browse | Angelo Corti Fabrizio Marcucci Ronald Berenson |
| author_facet | Ronald Berenson Angelo Corti Fabrizio Marcucci |
| author_sort | Ronald Berenson |
| collection | Directory of Open Access Books |
| description | The main scope of this topic is to give an update on pharmacologic and non-pharmacologic approaches to enhance uptake and penetration of cancer drugs into tumors. Inadequate accumulation of drugs in tumors has emerged over the last decade as one of the main problems underlying therapeutic failure and drug resistance in the treatment of cancer. Insufficient drug uptake and penetration is causally related to the abnormal tumor architecture. Thus, poor vascularization, increased resistance to blood flow and impaired blood supply represent a first obstacle to the delivery of antitumor drugs to tumor tissue. Decreased or even inverted transvascular pressure gradients compromise convective delivery of drugs. Eventually, an abnormal extracellular matrix offers increased frictional resistance to tumor drug penetration. Abnormal tumor architecture also changes the biology of tumor cells, which contributes to drug resistance through several different mechanisms. The variability in vessel location and structure can make many areas of the tumor hypoxic, which causes the tumor cells to become quiescent and thereby resistant to many antitumor drugs. In addition, the abnormally long distance of part of the tumor cell population from blood vessels provides a challenge to delivering cancer drugs to these cells. We have recently proposed additional mechanisms of tumor drug resistance, which are also related to abnormal tumor architecture. First, increased interstitial fluid pressure can by itself induce drug resistance through the induction of resistance-promoting paracrine factors. Second, the interaction of drug molecules with vessel- proximal tumor cell layers may also induce the release of these factors, which can spread throughout the cancer, and induce drug resistance in tumor cells distant from blood vessels. As can be seen, abnormal tumor architecture, inadequate drug accumulation and tumor drug resistance are tightly linked phenomena, suggesting the need to normalize the tumor architecture, including blood vessels, and/or increase the accumulation of cancer drugs in tumors in order to increase therapeutic effects. Indeed, several classes of drugs (that we refer to as promoter drugs) have been described, that promote tumor uptake and penetration of antitumor drugs, including those that are vasoactive, modify the barrier function of tumor vessels, debulk tumor cells, and overcome intercellular and stromal barriers. In addition, also non-pharmacologic approaches have been described that enhance tumor accumulation of effector drugs (e.g. convection-enhanced delivery, hyperthermia, etc.). Some drugs that have already received regulatory approval (e.g. the anti-VEGF antibody bevacizumab) exert antitumor effects at least in part through normalization of the tumor vasculature and enhancement of the accumulation of effector drugs. Other drugs, acting through different mechanisms of action, are now in clinical development (e.g. NGR-TNF in phase II/III studies) and others are about to enter clinical investigation (e.g. JO-1). |
| format | Online |
| id | doab-20.500.12854ir-62540 |
| institution | Directory of Open Access Books |
| language | eng |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| publisher | Frontiers Media SA |
| publisherStr | Frontiers Media SA |
| record_format | ojs |
| spelling | doab-20.500.12854ir-625402024-03-31T13:10:16Z Ways to improve tumor uptake and penetration of drugs into solid tumors Ronald Berenson Angelo Corti Fabrizio Marcucci R5-920 RM1-950 RC254-282 Q1-390 Resistance microenvironment Administration targeting Penetration Drug delivery Permeability Junctions Cancer Integrins thema EDItEUR::M Medicine and Nursing The main scope of this topic is to give an update on pharmacologic and non-pharmacologic approaches to enhance uptake and penetration of cancer drugs into tumors. Inadequate accumulation of drugs in tumors has emerged over the last decade as one of the main problems underlying therapeutic failure and drug resistance in the treatment of cancer. Insufficient drug uptake and penetration is causally related to the abnormal tumor architecture. Thus, poor vascularization, increased resistance to blood flow and impaired blood supply represent a first obstacle to the delivery of antitumor drugs to tumor tissue. Decreased or even inverted transvascular pressure gradients compromise convective delivery of drugs. Eventually, an abnormal extracellular matrix offers increased frictional resistance to tumor drug penetration. Abnormal tumor architecture also changes the biology of tumor cells, which contributes to drug resistance through several different mechanisms. The variability in vessel location and structure can make many areas of the tumor hypoxic, which causes the tumor cells to become quiescent and thereby resistant to many antitumor drugs. In addition, the abnormally long distance of part of the tumor cell population from blood vessels provides a challenge to delivering cancer drugs to these cells. We have recently proposed additional mechanisms of tumor drug resistance, which are also related to abnormal tumor architecture. First, increased interstitial fluid pressure can by itself induce drug resistance through the induction of resistance-promoting paracrine factors. Second, the interaction of drug molecules with vessel- proximal tumor cell layers may also induce the release of these factors, which can spread throughout the cancer, and induce drug resistance in tumor cells distant from blood vessels. As can be seen, abnormal tumor architecture, inadequate drug accumulation and tumor drug resistance are tightly linked phenomena, suggesting the need to normalize the tumor architecture, including blood vessels, and/or increase the accumulation of cancer drugs in tumors in order to increase therapeutic effects. Indeed, several classes of drugs (that we refer to as promoter drugs) have been described, that promote tumor uptake and penetration of antitumor drugs, including those that are vasoactive, modify the barrier function of tumor vessels, debulk tumor cells, and overcome intercellular and stromal barriers. In addition, also non-pharmacologic approaches have been described that enhance tumor accumulation of effector drugs (e.g. convection-enhanced delivery, hyperthermia, etc.). Some drugs that have already received regulatory approval (e.g. the anti-VEGF antibody bevacizumab) exert antitumor effects at least in part through normalization of the tumor vasculature and enhancement of the accumulation of effector drugs. Other drugs, acting through different mechanisms of action, are now in clinical development (e.g. NGR-TNF in phase II/III studies) and others are about to enter clinical investigation (e.g. JO-1). 2021-02-12T08:21:19Z 2021-02-12T08:21:19Z 2016-03-10 08:14:32 2014 book 18680 16648714 9782889193509 https://directory.doabooks.org/handle/20.500.12854/62540 eng Frontiers Research Topics image/jpeg Attribution 4.0 International http://www.frontiersin.org/books/Ways_to_improve_tumor_uptake_and_penetration_of_drugs_into_solid_tumors/390#nogo http://journal.frontiersin.org/researchtopic/1094/ways-to-improve-tumor-uptake-and-penetration-of-drugs-into-solid-tumors Frontiers Media SA 10.3389/978-2-88919-350-9 10.3389/978-2-88919-350-9 bf5ce210-e72e-4860-ba9b-c305640ff3ae 9782889193509 129 open access |
| spellingShingle | R5-920 RM1-950 RC254-282 Q1-390 Resistance microenvironment Administration targeting Penetration Drug delivery Permeability Junctions Cancer Integrins thema EDItEUR::M Medicine and Nursing Ronald Berenson Angelo Corti Fabrizio Marcucci Ways to improve tumor uptake and penetration of drugs into solid tumors |
| title | Ways to improve tumor uptake and penetration of drugs into solid tumors |
| title_full | Ways to improve tumor uptake and penetration of drugs into solid tumors |
| title_fullStr | Ways to improve tumor uptake and penetration of drugs into solid tumors |
| title_full_unstemmed | Ways to improve tumor uptake and penetration of drugs into solid tumors |
| title_short | Ways to improve tumor uptake and penetration of drugs into solid tumors |
| title_sort | ways to improve tumor uptake and penetration of drugs into solid tumors |
| topic | R5-920 RM1-950 RC254-282 Q1-390 Resistance microenvironment Administration targeting Penetration Drug delivery Permeability Junctions Cancer Integrins thema EDItEUR::M Medicine and Nursing |
| topic_facet | R5-920 RM1-950 RC254-282 Q1-390 Resistance microenvironment Administration targeting Penetration Drug delivery Permeability Junctions Cancer Integrins thema EDItEUR::M Medicine and Nursing |
| url | 18680 |
| work_keys_str_mv | AT ronaldberenson waystoimprovetumoruptakeandpenetrationofdrugsintosolidtumors AT angelocorti waystoimprovetumoruptakeandpenetrationofdrugsintosolidtumors AT fabriziomarcucci waystoimprovetumoruptakeandpenetrationofdrugsintosolidtumors |