Inducing Angiogenesis, a Key Step in Cancer Vascularization, and Treatment Approaches

Saman, Harman; Raza, Syed Shadab; Uddin, Shahab; Rasul, Kakil Ibrahim

doi:10.3390/cancers12051172

Cited by 119 publications

(76 citation statements)

References 115 publications

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“…These findings suggested that STAT-3 might be a promising therapeutic target for cancer treatment with few side effects. The vascular endothelial growth factor (VEGF), originally known as the vascular permeability factor (VPF), is a signal protein that can stimulate the formation of blood vessels in cancer development [42]. Sim et al showed that STAT-3 could regulate the expression of VEGF in various types of cancers [43].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Genipin suppression of growth and metastasis in hepatocellular carcinoma through blocking activation of STAT-3

Hong

Lee

Clayton

et al. 2020

J Exp Clin Cancer Res

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Background: The signal transducer and activator of transcription-3 (STAT-3) can facilitate cancer progression and metastasis by being constitutively active via various signaling. Abundant evidence has indicated that STAT-3 may be a promising molecular target for cancer treatment. Methods: In this study, a dual-luciferase assay-based screening of 537 compounds for STAT-3 inhibitors of hepatocellular carcinoma (HCC) cells was conducted, leading to the identification of genipin. Effects of genipin on HCC were assessed in a patient-derived xenograft nude mice model. Western blotting assay, chromatin immunoprecipitation (ChIP) assay, molecular docking study, tube formation assay, three-dimensional top culture assay, histological examination, and immunofluorescence were utilized to evaluate the regulatory signaling pathway. Results: Our research demonstrated that genipin suppresses STAT-3 phosphorylation and nuclear translocation, which may be attributed to the binding capacity of this compound to the Src homology-2 (SH2) domain of STAT-3. In addition, the therapeutic effects of genipin in a patient-derived HCC xenograft nude mice model were also demonstrated. Conclusions: In conclusion, genipin showed therapeutic potential for HCC treatment by interacting with the SH2-STAT-3 domain and suppressing the activity of STAT-3. In the future, further research is planned to explore the potential role of genipin in combination with chemotherapy or radiotherapy for HCC.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Genipin suppression of growth and metastasis in hepatocellular carcinoma through blocking activation of STAT-3

Hong

Lee

Clayton

et al. 2020

J Exp Clin Cancer Res

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“…VEGF-A and VEGFRs are well-characterized targets for antiangiogenic therapeutics and these drugs have shown a varying range of effectiveness across tumor types [272]. Monoclonal antibodies such as Bevacizumab (Avastin), a humanized monoclonal antibody that blocks VEGF-A, or small molecules such as vandetanib, which inhibits tyrosine kinases downstream of VEGF, are examples of anti-VEGF treatment.…”

Section: Therapeutic Targets Regulated By Tgli1mentioning

confidence: 99%

Hedgehog Signaling and Truncated GLI1 in Cancer

Doheny

Manore

Wong

et al. 2020

Cells

128

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The hedgehog (HH) signaling pathway regulates normal cell growth and differentiation. As a consequence of improper control, aberrant HH signaling results in tumorigenesis and supports aggressive phenotypes of human cancers, such as neoplastic transformation, tumor progression, metastasis, and drug resistance. Canonical activation of HH signaling occurs through binding of HH ligands to the transmembrane receptor Patched 1 (PTCH1), which derepresses the transmembrane G protein-coupled receptor Smoothened (SMO). Consequently, the glioma-associated oncogene homolog 1 (GLI1) zinc-finger transcription factors, the terminal effectors of the HH pathway, are released from suppressor of fused (SUFU)-mediated cytoplasmic sequestration, permitting nuclear translocation and activation of target genes. Aberrant activation of this pathway has been implicated in several cancer types, including medulloblastoma, rhabdomyosarcoma, basal cell carcinoma, glioblastoma, and cancers of lung, colon, stomach, pancreas, ovarian, and breast. Therefore, several components of the HH pathway are under investigation for targeted cancer therapy, particularly GLI1 and SMO. GLI1 transcripts are reported to undergo alternative splicing to produce truncated variants: loss-of-function GLI1ΔN and gain-of-function truncated GLI1 (tGLI1). This review covers the biochemical steps necessary for propagation of the HH activating signal and the involvement of aberrant HH signaling in human cancers, with a highlight on the tumor-specific gain-of-function tGLI1 isoform.

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“…Angiogenesis is an essential process in tumor development and metastatic spread, as it constantly supplies tumor mass with oxygen and nutrients [ 101 ]. In this context, several reports have provided evidence that the endothelial cells of the surrounding tumor stroma express FGFRs that mediate the stimulatory action of FGFs [ 102 , 103 ].…”

Section: The Functional Interplay Between Fgf/fgfr Signaling and Bmentioning

confidence: 99%

The FGF/FGFR System in Breast Cancer: Oncogenic Features and Therapeutic Perspectives

Santolla

Maggiolini

2020

Cancers

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One of the major challenges in the treatment of breast cancer is the heterogeneous nature of the disease. With multiple subtypes of breast cancer identified, there is an unmet clinical need for the development of therapies particularly for the less tractable subtypes. Several transduction mechanisms are involved in the progression of breast cancer, therefore making the assessment of the molecular landscape that characterizes each patient intricate. Over the last decade, numerous studies have focused on the development of tyrosine kinase inhibitors (TKIs) to target the main pathways dysregulated in breast cancer, however their effectiveness is often limited either by resistance to treatments or the appearance of adverse effects. In this context, the fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) system represents an emerging transduction pathway and therapeutic target to be fully investigated among the diverse anti-cancer settings in breast cancer. Here, we have recapitulated previous studies dealing with FGFR molecular aberrations, such as the gene amplification, point mutations, and chromosomal translocations that occur in breast cancer. Furthermore, alterations in the FGF/FGFR signaling across the different subtypes of breast cancer have been described. Next, we discussed the functional interplay between the FGF/FGFR axis and important components of the breast tumor microenvironment. Lastly, we pointed out the therapeutic usefulness of FGF/FGFR inhibitors, as revealed by preclinical and clinical models of breast cancer.

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Inducing Angiogenesis, a Key Step in Cancer Vascularization, and Treatment Approaches

Cited by 119 publications

References 115 publications

RETRACTED ARTICLE: Genipin suppression of growth and metastasis in hepatocellular carcinoma through blocking activation of STAT-3

RETRACTED ARTICLE: Genipin suppression of growth and metastasis in hepatocellular carcinoma through blocking activation of STAT-3

Hedgehog Signaling and Truncated GLI1 in Cancer

The FGF/FGFR System in Breast Cancer: Oncogenic Features and Therapeutic Perspectives

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