Clinical strategies to inhibit tumor vascularization

Harris, Adrian L.

doi:10.1016/b978-0-12-819494-2.00009-2

Cited by 2 publications

(6 citation statements)

References 123 publications

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“…Targeting VEGF signal transduction with tyrosine kinase inhibitors is another strategy, but results in metastatic breast cancer are also disappointing (121). Although suppressing the VEGF pathway indeed decreases vascular density, rapid revascularization occurs within 2 weeks as shown in a neoadjuvant window-of-opportunity bevacizumab study (5,39,119). This is likely mediated through induction of hypoxia by the anti-angiogenic therapy, resulting in compensatory upregulation of both VEGF and VEGF-independent angiogenesis pathways (119,122).…”

Section: Therapeutic Strategies Targeting Angiogenesismentioning

confidence: 99%

“…This is likely mediated through induction of hypoxia by the anti-angiogenic therapy, resulting in compensatory upregulation of both VEGF and VEGF-independent angiogenesis pathways (119,122). Proposed resistance mechanisms include vascular mimicry, enhancement of invasive potential, recruitment of bone marrow-derived precursor endothelial cells, and promotion of alternative proangiogenic pathways (5,39,42,123), which are of interest as potential therapeutic targets in breast cancer.…”

Section: Therapeutic Strategies Targeting Angiogenesismentioning

confidence: 99%

“…the growth of new blood vessels from pre-existing vasculature. Targeting of key players in metabolic and angiogenic pathways in breast cancer has yielded disappointing results, the most notable being the lack of overall survival benefit of the anti-angiogenic agent bevacizumab that targets VEGF (5).…”

Section: Introductionmentioning

confidence: 99%

“…It was subsequently reasoned that only patients with especially deregulated and wide-spread tumor microvasculature might benefit from bevacizumab-induced vessel normalization. However, in retrospective analyses, intuitively logical biomarkers correlated with pCR rates and normalization of tumor vasculature in some cases but did not predict final clinical outcomes.Evaluated biomarkers include high baseline MVD, high volume transfer constant on dynamic contrast-enhanced MRI (DCE-MRI), elevated expression of pro-angiogenic factors (e.g.VEGF(R) andTie2 measured immunohistochemically or in patients' serum) and, more recently, NDRG1 and panels representing DNA methylation status or hypoxia gene sets in HER2-negative breast cancer patients on neoadjuvant bevacizumab + chemotherapy(5,80,(117)(118)(119). Multiple alternative vascular markers are being evaluated in different cancer types, e.g.…”

mentioning

confidence: 99%

“…Multiple alternative vascular markers are being evaluated in different cancer types, e.g. the vascular co-option players stromal derived factor 1 and CXCR4, and ANGPT2(5,39).…”

mentioning

confidence: 99%

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HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

Heer¹,

Jalving²,

Harris³

2020

Journal of Clinical Investigation

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238

146

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Hypoxia-inducible factors (HIFs) and the HIF-dependent cancer hallmarks angiogenesis and metabolic rewiring are well-established drivers of breast cancer aggressiveness, therapy resistance, and poor prognosis. Targeting of HIF and its downstream targets in angiogenesis and metabolism has been unsuccessful so far in the breast cancer clinical setting, with major unresolved challenges residing in target selection, development of robust biomarkers for response prediction, and understanding and harnessing escape mechanisms. This Review discusses the pathophysiological role of HIFs, angiogenesis, and metabolism in breast cancer and the challenges of targeting these features in breast cancer patients. Rational therapeutic combinations, especially with immunotherapy and endocrine therapy, seem most promising in the clinical exploitation of the intricate interplay of HIFs, angiogenesis, and metabolism in breast cancer cells and the tumor microenvironment.

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Section: Therapeutic Strategies Targeting Angiogenesismentioning

confidence: 99%

Section: Therapeutic Strategies Targeting Angiogenesismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

“…Multiple alternative vascular markers are being evaluated in different cancer types, e.g. the vascular co-option players stromal derived factor 1 and CXCR4, and ANGPT2(5,39).…”

mentioning

confidence: 99%

See 3 more Smart Citations

HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

Heer¹,

Jalving²,

Harris³

2020

Journal of Clinical Investigation

Self Cite

238

146

View full text Add to dashboard Cite

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Analyses of hypoxia-related risk factors and clinical relevance in breast cancer

Li,

Yu,

Han

et al. 2024

Front. Oncol.

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IntroductionHypoxia plays an important role in the heterogeneity, relapse, metastasis, and drug resistance of breast cancer. In this study, we explored the hypoxia-related biological signatures in different subtypes of breast cancer and identified the key prognostic factors by bioinformatics methods.MethodsBased on The Cancer Genome Atlas (TCGA) Breast Cancer datasets, we divided the samples into immune-activated/suppressed populations by single-sample gene set enrichment analysis (ssGSEA) and then used hierarchical clustering to further identify hypoxic/non-hypoxic populations from the immune-suppressed samples. A hypoxia related risk model of breast cancer was constructed.ResultsNuclear factor interleukin-3 regulated (NFIL3), serpin family E member 1 (SERPINE1), FOS, biglycan (BGN), epidermal growth factor receptor (EGFR), and sushi-repeat-containing protein, X-linked (SRPX) were identified as key hypoxia-related genes. Margin status, American Joint Committee on Cancer (AJCC) stage, hypoxia status, estrogen receptor/progesterone receptor (ER/PR) status, NFIL3, SERPINE1, EGFR, and risk score were identified as independent prognostic indicators for breast cancer patients. The 3- and 5-year survival curves of the model and immunohistochemical staining on the breast cancer microarray verified the statistical significance and feasibility of our model. Among the different molecular types of breast cancer, ER/PR+ and HER2+ patients might have higher hypoxia-related risk scores. ER/PR-negative samples demonstrated more activated immune-related pathways and better response to most anticancer agents.DiscussionOur study revealed a novel risk model and potential feasible prognostic factors for breast cancer and might provide new perspectives for individual breast cancer treatment.

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Clinical strategies to inhibit tumor vascularization

Cited by 2 publications

References 123 publications

HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

Analyses of hypoxia-related risk factors and clinical relevance in breast cancer

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