Angiogenesis and Anti-Angiogenic Treatment in Prostate Cancer: Mechanisms of Action and Molecular Targets

Ioannidou, Evangelia; Moschetta, Michele; Shah, Sidrah; Parker, Jack Steven; Ozturk, Mehmet Akif; Pappas-Gogos, George; Sheriff, Matin; Rassy, Elie El; Boussios, Stergios

doi:10.3390/ijms22189926

Cited by 50 publications

(26 citation statements)

References 148 publications

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“…However, clinical efficacy of VEGFtargeted drugs has vital limitations. Although phase 3 trials have demonstrated that use of anti-angiogenic agents leads to significant improvements in overall survival (OS) for several cancers, such as advanced-stage CRC, RCC, and HCC, it is also associated with a failure to improve OS in other cancers, such as breast cancer, glioblastoma, pancreatic ductal adenocarcinoma (PDAC) and prostate cancer (10)(11)(12)(13). Carvalho B et al discovered that, in glioblastoma, c-Met overexpression is associated with a time-to-progression (TTP) after bevacizumab of 3 months (95% CI, 1.5-4.5), compared with a TTP of 7 months (95% CI, 4.6-9.4) among patients with low or no expression of c-Met (p = 0.05).…”

Section: The Resistance To Antiangiogenic Therapymentioning

confidence: 99%

The Research Progress of Antiangiogenic Therapy, Immune Therapy and Tumor Microenvironment

Chen

Tan

et al. 2022

Front. Immunol.

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Anti-angiogenesis therapy, a promising strategy against cancer progression, is limited by drug-resistance, which could be attributed to changes within the tumor microenvironment. Studies have increasingly shown that combining anti-angiogenesis drugs with immunotherapy synergistically inhibits tumor growth and progression. Combination of anti-angiogenesis therapy and immunotherapy are well-established therapeutic options among solid tumors, such as non-small cell lung cancer, hepatic cell carcinoma, and renal cell carcinoma. However, this combination has achieved an unsatisfactory effect among some tumors, such as breast cancer, glioblastoma, and pancreatic ductal adenocarcinoma. Therefore, resistance to anti-angiogenesis agents, as well as a lack of biomarkers, remains a challenge. In this review, the current anti-angiogenesis therapies and corresponding drug-resistance, the relationship between tumor microenvironment and immunotherapy, and the latest progress on the combination of both therapeutic modalities are discussed. The aim of this review is to discuss whether the combination of anti-angiogenesis therapy and immunotherapy can exert synergistic antitumor effects, which can provide a basis to exploring new targets and developing more advanced strategies.

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Section: The Resistance To Antiangiogenic Therapymentioning

confidence: 99%

The Research Progress of Antiangiogenic Therapy, Immune Therapy and Tumor Microenvironment

Chen

Tan

et al. 2022

Front. Immunol.

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“…We sequenced RNA from 52,680 cells at eight time points (stem cells -1, 3, 4, 5, 6, 7, 14 and 21 days of differentiation, pooling 20-30 aggregates or 15-20 organoids per time point) (Table S1). At each time point, we combined and dissociated tissues from both cell lines together, and subsequently demultiplexed the sequencing data using single nucleotide polymorphisms (SNPs) differing between the two individuals (demuxlet (Kang et al, 2018)). After quality control, we integrated the datasets using cluster similarity spectrum (CSS (He et al, 2020)) and visualized cell transcriptomes in a Uniform Manifold Approxima- tion and Projection (UMAP (McInnes et al, 2018)) embedding (Fig.…”

Section: Resultsmentioning

confidence: 99%

Fate and state transitions during human blood vessel organoid development

Nikolova

Wimmer

et al. 2022

Preprint

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Blood vessel organoids (BVOs) derived from human pluripotent stem cells have emerged as a novel system to understand human vascular development, model disorders, and develop regenerative therapies. However, it is unclear which molecular states constitute BVOs and how cells differentiate and self-organize within BVOs in vitro and after transplantation. Here we reconstruct BVO development over a time course using single-cell transcriptomics. We observe progenitor states that bifurcate into endothelial and mural fates, and find that BVOs do not acquire definitive arterio-venous endothelial identities in vitro. Chromatin accessibility profiling identifies gene regulatory network (GRN) features associated with endothelial and mural fate decisions, and transcriptome-coupled lineage recording reveals multipotent progenitor states within BVOs. We perform single-cell genetic perturbations within mosaic BVOs to dissect the impact of transcription factor (TF) and receptor depletion on cell differentiation, and highlight multiple TFs including MECOM and ETV2 as strong-effect regulators of human BVO development. We show that manipulation of VEGF and Notch signaling pathways alters BVO morphogenesis and endothelial GRNs, and induces arteriovenous-like state differentiation. We analyze matured BVOs after transplantation using scRNA-seq, and observe matured endothelium with clear arteriovenous specification. We also observe off-target cell fates with bone and adipocyte features, suggesting multipotent states reside within the BVOs in vitro that expand and diversify in less restrictive conditions. Finally, we map vascular disease associated genes to BVO cell states to highlight the potential of BVOs for disease modeling. Altogether, our data and analyses provide the first comprehensive cell state atlas of BVO development and illuminate both the power and limitation of BVOs for translational research.

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“…MiRNAs could regulate endothelial cells via non-cell-autonomous, as well as cell-autonomous techniques, and therefore control angiogenesis and PCa progression. 55 Thus, single miRNAs or miRNA expression profiles could be potential biomarkers for PCa based on their stability and detectability in biopsy tissue and body fluids. 56 , 57 In this study, we selected seven miRNAs that were involved in PCa.…”

Section: Discussionmentioning

confidence: 99%

miR-145-5p: A Potential Biomarker in Predicting Gleason Upgrading of Prostate Biopsy Samples Scored 3+3=6

Wang¹,

Dong²,

Sun³

et al. 2021

CMAR

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Background The Gleason grading system is a major tool used for prediction of prostate cancer (PCa) behavior. Because of heterogeneity and sampling errors, prognosis is variable even among patients with the same Gleason score (GS). Therefore, more accurate biomarkers that complement the Gleason system are needed to improve the clinical management of PCa. Methods Formalin-fixed, paraffin embedded tissue samples were obtained from radical prostatectomy (RP) (patient set 1, n=53) and needle biopsy (patient set 2, n=107; patient set 3, n=119). Cancer tissues from pure regions of each Gleason pattern (GP) were separately collected using laser-captured microdissection, followed by Real-time-PCR to determine the relative expression of miRNAs, including miR-1-5p, miR-21-5p, miR-30d-5p, miR-100-5p, miR-145-5p, miR-224-5p, and miR-708-5p. miRNA’s association with Gleason upgrading (GU) was evaluated using receiver operator characteristics (ROC) curve and multivariate logistic regression analysis. The integrated miRNA targets prediction and enrichment analyses were performed to determine the potential functions of miRNA. Results It was found that miR-145-5p in GP3 from radical prostatectomy (RP) were overexpressed in patients with GS6 PCa compared with GS7 patients, which was further confirmed in a larger biopsy cohort. ROC curve analysis revealed that miR-145-5p in biopsy was significantly associated with GU upon RP. In multivariate analyses, miR-145-5p was an independent predictor of GU. Conclusion Our study indicated that differential expression of miRNAs existed in GP3 from pure GS6 and GS7 PCa, highlighting a path toward the clinical use of miRNAs in predicting GU and assisting in treatment modality selection.

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Angiogenesis and Anti-Angiogenic Treatment in Prostate Cancer: Mechanisms of Action and Molecular Targets

Cited by 50 publications

References 148 publications

The Research Progress of Antiangiogenic Therapy, Immune Therapy and Tumor Microenvironment

The Research Progress of Antiangiogenic Therapy, Immune Therapy and Tumor Microenvironment

Fate and state transitions during human blood vessel organoid development

miR-145-5p: A Potential Biomarker in Predicting Gleason Upgrading of Prostate Biopsy Samples Scored 3+3=6

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