Emergence of potential biomarkers of response to anti‐angiogenic anti‐tumour agents

Michael, Agnieszka; Relph, Kate; Pandha, Hardev

doi:10.1002/ijc.25389

Cited by 11 publications

(7 citation statements)

References 117 publications

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“…It would have been helpful to measure TK in a large group of healthy control animals in the hospital, however, financial limitations made this impossible in this study. Practical use of tumour biomarkers is often hampered by their lack of specificity, generally because of measurable levels of the marker in normal individuals or those with benign disease 29–32 . Therefore, the upper end of the reference interval must be sufficiently high to avoid an unacceptable false positive rate 33 .…”

Section: Discussionmentioning

confidence: 99%

Thymidine kinase assay in canine lymphoma

Elliott

Cripps

Blackwood

2011

Vet Comparative Oncology

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The aim of the study was to evaluate if thymidine kinase (TK) correlated with duration of first remission (DFR) or survival in dogs with lymphoma and if initial TK levels correlated with stage and substage; and also to assess if TK level at diagnosis correlated with immunophenotype. TK was assayed in 73 dogs with treatment naïve lymphoma, then again after treatment; 47% had an initial TK above the reference interval. Dogs with B-cell lymphoma had higher initial TK activities than dogs with T-cell lymphoma. TK levels were not higher in dogs with higher stage disease and TK activity prior to treatment was not associated with DFR or survival. Where TK was elevated at diagnosis, it fell into the reference range during remission. TK was normal in 53% dogs at diagnosis, which is higher than previously reported. Further studies are warranted to assess the utility of TK in dogs with lymphoma.

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Section: Discussionmentioning

confidence: 99%

Thymidine kinase assay in canine lymphoma

Elliott

Cripps

Blackwood

2011

Vet Comparative Oncology

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“…However, this correlation has not been seen in other tumors [113]. Dynamic contrast-enhanced Doppler ultrasound with perfusion software and contrast agent injection may be a good noninvasive predictive factor of progression-free survival (PFS) of sorafenib [114].…”

Section: Current Biomarkers For the Monitoring Of Antiangiogenic Therapymentioning

confidence: 99%

“…Low concentrations of soluble IL-2 receptors (sIL-2R) during antiangiogenic therapy seemed also predictive of benefit to treatment [127]. However, as sIL-2R is also a prognostic marker for clinical outcome, it has to be determined if its value is really related to response to therapy or to its role as a prognostic factor [113,128,129] .…”

Section: Immune Parameters As An Emergent Class Of Biomarkers During mentioning

confidence: 99%

Angiogenesis and immunity: a bidirectional link potentially relevant for the monitoring of antiangiogenic therapy and the development of novel therapeutic combination with immunotherapy

Tartour

Péré

Maillère

et al. 2011

Cancer Metastasis Rev

279

205

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The immune system regulates angiogenesis in cancer with both pro- and antiangiogenic activities. The induction of angiogenesis is mediated by tumor-associated macrophages and myeloid-derived suppressor cells (MDSC) which produce proinflammatory cytokines, endothelial growth factors (VEGF, bFGF…), and protease (MMP9) implicated in neoangiogenesis. Some cytokines (IL-6, IL-17…) activated Stat3 which also led to the production of VEGF and bFGF. In contrast, other cytokines (IFN, IL-12, IL-21, and IL-27) display an antiangiogenic activity. Recently, it has been shown that some antiangiogenic molecules alleviates immunosuppression associated with cancer by decreasing immunosuppressive cells (MDSC, regulatory T cells), immunosuppressive cytokines (IL-10, TGFβ), and inhibitory molecules on T cells (PD-1). Some of these broad effects may result from the ability of some antiangiogenic molecules, especially cytokines to inhibit the Stat3 transcription factor. The association often observed between angiogenesis and immunosuppression may be related to hypoxia which induces both neoangiogenesis via activation of HIF-1 and VEGF and favors the intratumor recruitment and differentiation of regulatory T cells and MDSC. Preliminary studies suggest that modulation of immune markers (intratumoral MDSC and IL-8, peripheral regulatory T cells…) may predict clinical response to antiangiogenic therapy. In preclinical models, a synergy has been observed between antiangiogenic molecules and immunotherapy which may be explained by an improvement of immune status in tumor-bearing mice after antiangiogenic therapy. In preclinical models, antiangiogenic molecules promoted intratumor trafficking of effector cells, enhance endogenous anti-tumor response, and synergyzed with immunotherapy protocols to cure established murine tumors. All these results warrant the development of clinical trials combining antiangiogenic drugs and immunotherapy.

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“…In contrast, a higher level of EPCs before treatment has implied a higher incidence of death . Thus, EPC is being considered as a surrogate biomarker for monitoring cancer progression, predicting disease‐free survival as well as optimizing efficacy of antiangiogenic therapy . These observations strengthen the hypothesis that EPCs may be a feasible target against NSCLC neovascularization …”

Section: Discussionmentioning

confidence: 76%

Endothelial progenitor cells contribute to neovascularization of non‐small cell lung cancer via histone deacetylase 7‐mediated cytoskeleton regulation and angiogenic genes transcription

Zhou

et al. 2018

Intl Journal of Cancer

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To supply tumor tissues with nutrients and oxygen, endothelial progenitor cells (EPCs) home to tumor sites and contribute to neovascularization. Although the precise mechanism of EPCs-induced neovascularization remains poorly understood in non-small cell lung cancer (NSCLC), histone deacetylase 7 (HDAC7) is considered as a critical regulator. To explore the function of HDAC7 in neovascularization induced by EPCs, tube formation assay, immunofluorescence, microarray, Western blot analysis and animal models were performed. In vitro, HDAC7 abrogation led to the activation of Rho-associated coiled-coil containing protein kinase/myosin light chain 2 pathway concomitant with ERK dephosphorylation, causing the instability of cytoskeleton and collapse of tube formation. In vivo, absence of HDAC7 impaired the vascular lumen integrity and decreased the functional blood perfusion, inhibiting the growth of tumor. At the level of transcription, HDAC7 silencing upregulated antiangiogenic genes and suppressed proangiogenic genes collectively, turning off the angiogenic switch during vessel formation. Taken together, HDAC7 plays a dual role in maintaining the structural and nonstructural functions of EPCs. Our work demonstrates the molecular mechanism by which HDAC7 contributes to the angiogenic property of EPCs and provides a rational basis for specific targeting of antiangiogenic strategies in lung cancer.

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Emergence of potential biomarkers of response to anti‐angiogenic anti‐tumour agents

Cited by 11 publications

References 117 publications

Thymidine kinase assay in canine lymphoma

Thymidine kinase assay in canine lymphoma

Angiogenesis and immunity: a bidirectional link potentially relevant for the monitoring of antiangiogenic therapy and the development of novel therapeutic combination with immunotherapy

Endothelial progenitor cells contribute to neovascularization of non‐small cell lung cancer via histone deacetylase 7‐mediated cytoskeleton regulation and angiogenic genes transcription

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