2020
DOI: 10.3390/diagnostics10020078
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Predicting Clinical Efficacy of Vascular Disrupting Agents in Rodent Models of Primary and Secondary Liver Cancers: An Overview with Imaging-Histopathology Correlation

Abstract: Vascular disrupting agents (VDAs) have entered clinical trials for over 15 years. As the leading VDA, combretastatin A4 phosphate (CA4P) has been evaluated in combination with chemotherapy and molecular targeting agents among patients with ovarian cancer, lung cancer and thyroid cancer, but still remains rarely explored in human liver cancers. To overcome tumor residues and regrowth after CA4P monotherapy, a novel dual targeting pan-anticancer theragnostic strategy, i.e., OncoCiDia, has been developed and show… Show more

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Cited by 11 publications
(13 citation statements)
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References 81 publications
(230 reference statements)
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“…Widespread DCE investigations were used in the development of the combretastatins (CA4P and CA1P) as well as DMXAA and ZD6126) [ 5 , 27 , 37 , 96 , 97 , 100 , 102 , 103 , 104 , 106 , 117 , 124 , 125 , 126 , 127 , 128 , 131 , 132 , 135 , 136 , 137 , 138 , 219 , 220 , 221 ] and continue to be popular in pre-clinical development ( Table 3 ), since they may also be implemented readily in clinical trials ( Table 1 ). Examples of parametric images derived from DCE-MRI are presented in Figure 7 , where tumor heterogeneity is apparent at baseline, as well as in response to the novel vascular disrupting agent OXi6197, the phosphate prodrug of OXi6196 ( Figure 2 A) a dihydronaphthalene analog of combretastatin.…”
Section: Imaging Technologiesmentioning
confidence: 99%
See 1 more Smart Citation
“…Widespread DCE investigations were used in the development of the combretastatins (CA4P and CA1P) as well as DMXAA and ZD6126) [ 5 , 27 , 37 , 96 , 97 , 100 , 102 , 103 , 104 , 106 , 117 , 124 , 125 , 126 , 127 , 128 , 131 , 132 , 135 , 136 , 137 , 138 , 219 , 220 , 221 ] and continue to be popular in pre-clinical development ( Table 3 ), since they may also be implemented readily in clinical trials ( Table 1 ). Examples of parametric images derived from DCE-MRI are presented in Figure 7 , where tumor heterogeneity is apparent at baseline, as well as in response to the novel vascular disrupting agent OXi6197, the phosphate prodrug of OXi6196 ( Figure 2 A) a dihydronaphthalene analog of combretastatin.…”
Section: Imaging Technologiesmentioning
confidence: 99%
“…Acute vascular shutdown is the most obvious early effect revealed by MRI. Later effects may also be examined such as using diffusion-weighted imaging (DWI) to observe changes in cell structure, whereby diffusion is restricted in well-structured tissue, but becomes more mobile with necrosis, which occurs extensively within 24 h after VDA [ 98 , 102 , 104 , 117 , 219 , 222 ]. MR Elastography indicated reduction in tumor viscoelasticity 24 h after ZD6126 at which time no significant change in tumor apparent diffusion coefficient (ADC) was observed [ 228 ].…”
Section: Imaging Technologiesmentioning
confidence: 99%
“…Acute vascular shutdown is the most obvious early effect revealed by MRI. Later effects may also be examined such as using diffusion-weighted imaging (DWI) to observe changes in cell structure, whereby diffusion is restricted in well-structured tissue, but becomes more mobile with necrosis, which occurs extensively within 24 hrs after VDA [98,102,104,116,211,214]. MR Elastography indicated reduction in tumor viscoelasticity 24 hrs after ZD6126 at which time no significant change in tumor apparent diffusion coefficient (ADC) was observed [220].…”
Section: Magnetic Resonance Imaging (Mri)mentioning
confidence: 99%
“…Originally isolated from the bark of the South African willow tree Combretum caffrum [6], CA-4 is one of the most potent inhibitors of tubulin polymerization, which interferes with microtubule dynamics and perturbs the mitotic cycle [7,8]. CA-4 selectively inhibits tumor neovascularization, causing rapid vascular shutdown and tumor necrosis [9,10]. When administered in vivo, CA-4 causes disruption and collapse of tumor blood vessels and subsequent necrotic cell death of tumor cells due to the lack of oxygen and nutrients [11][12][13].…”
Section: Introductionmentioning
confidence: 99%