Angiogenesis in endometrial carcinoma: Therapies and biomarkers, current options, and future perspectives

Berger, Amnon A; Dao, Fanny; Levine, Douglas A.

doi:10.1016/j.ygyno.2020.12.016

Cited by 24 publications

(29 citation statements)

References 45 publications

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“…Angiogenesis is one of the hallmarks of cancer according to Hanahan and Weinberg [ 14 ] playing a crucial role in the progression of EC. One of the most important proangiogenic factors is the Vascular Endothelial Growth Factor (VEGF) [ 229 ]. VEGF is often targeted in novel therapies including anti-VEGF antibody (bevacizumab), VEGF trap (aflibercept), or Tyrosine Kinase Inhibitors (TKI).…”

Section: Discussionmentioning

confidence: 99%

“…Therapy with bevacizumab was approved by FDA in different tumors including colorectal cancer and is currently tested in EC [ 229 , 230 ]. An increased number of clinical trials are assessing the efficacy of that novel therapies in monotherapy as well as in a combination with other applied therapies but still lacks a personalized approach [ 229 ]. In this study, we found two miRNAs (miR-29a-5p and miR-545-3p) that target VEGF and thus influence EC progression.…”

Section: Discussionmentioning

confidence: 99%

“…VEGF is often targeted in novel therapies including anti-VEGF antibody (bevacizumab), VEGF trap (aflibercept), or Tyrosine Kinase Inhibitors (TKI). Therapy with bevacizumab was approved by FDA in different tumors including colorectal cancer and is currently tested in EC [229,230]. An increased number of clinical trials are assessing the efficacy of that novel therapies in monotherapy as well as in a combination with other applied therapies but still lacks a personalized approach [229].…”

Section: Angiogenesismentioning

confidence: 99%

See 2 more Smart Citations

The Role of miRNAs in the Regulation of Endometrial Cancer Invasiveness and Metastasis—A Systematic Review

Klicka

Grzywa

Klinke

et al. 2021

Cancers

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Endometrial cancer (EC) is the most common genital cancer in women with increasing death rates. MiRNAs are short non-coding RNAs that regulate gene expression on the post-transcriptional levels. Multiple studies demonstrated a fundamental role of miRNAs in the regulation of carcinogenesis. This systematic review is a comprehensive overview of the role of miRNAs in the regulation of cancer cell invasiveness and metastasis in EC. The literature was searched for studies investigating the role of miRNAs in the regulation of invasiveness and metastasis in EC. We explored PubMed, Embase, and Scopus using the following keywords: miRNA, metastasis, invasiveness, endometrial cancer. Data were collected from 163 articles that described the expression and role of 106 miRNAs in the regulation of EC invasiveness and metastasis out of which 63 were tumor suppressor miRNAs, and 38 were oncomiRNAs. Five miRNAs had a discordant role in different studies. Moreover, we identified 66 miRNAs whose expression in tumor tissue or concentration in serum correlated with at least one clinical parameter. These findings suggest a crucial role of miRNAs in the regulation of EC invasiveness and metastasis and present them as potential prognostic factors for patients with EC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Angiogenesismentioning

confidence: 99%

See 1 more Smart Citation

The Role of miRNAs in the Regulation of Endometrial Cancer Invasiveness and Metastasis—A Systematic Review

Klicka

Grzywa

Klinke

et al. 2021

Cancers

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“…EC is one of the most common gynecological malignancy and the fourth most prevalent cancer in women worldwide. 16 As the incidence and mortality of EC continue to increase, the burden of EC continues to increase compared to various cancers. 17 Although surgery is the mainstay of the treatment of EC, there are still 25% of the patients who are in an advanced stage of cancer at the time of surgery, with an expected 5-year survival rate of 40–70% for stage III patients, and an extremely poor 5-year survival rate of 0–10% for stage IV patients.…”

Section: Discussionmentioning

confidence: 99%

Fatty Acid–Binding Protein 4 (FABP4) Suppresses Proliferation and Migration of Endometrial Cancer Cells via PI3K/Akt Pathway

Jeong

Ren

et al. 2021

OTT

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Purpose Endometrial cancer (EC) is the sixth most common cancer in women and its incidence and mortality have been rising over the last decades. The latest research indicates that FABP4 plays a significant role in multiple types of cancer. But few studies were focused on EC. The aim of this article is to investigate whether FABP4 can suppress tumor growth and metastasis of EC via PI3K/Akt pathway to provide a novel therapeutic target for the treatment of EC. Materials and Methods FABP4 mRNA levels of EC were analysed through The Cancer Genome Atlas database (TCGA), and expression of FABP4 in EC cancer tissues was determined by immunohistochemistry (IHC) assays. Stable overexpressing cell lines were established using lentivirus infection to analyze the biological function of FABP4 in vitro. CCK8 assay and colony formation assay were performed to assess cell proliferation ability. Wound healing assay and transwell were performed to analyse migration and invasion of cells. The subcutaneous xenograft mouse model was used to evaluate tumor growth in vivo. Additionally, all protein levels were detected by Western blotting assay. Results We found that the expression of the FABP4 mRNA was decreased in tumor samples compared to normal tissue according to TCGA database analysis. Subsequent experimental mRNA and protein expression analysis confirmed that FABP4 expression was lower in EC tissue than normal endometrial tissue. In addition, we found overexpression of FABP4 inhibited the proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Further functional and mechanistic analysis of FABP4 demonstrated that its function is mediated by restraining the phosphorylation of PI3K/Akt signaling pathway. Conclusion Our studies shed light for the first time about the functional role of FABP4 in EC and provide a novel biomarker for EC as well as a therapeutic target for the therapy of EC.

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“…Anti-angiogenic agents have been successful in many cancer types but have generally shown disappointing results in EC to date. 60 Single agent bevacizumab (a monoclonal antibody against vascular endothelial growth factor-A) was assessed in recurrent or persistent EC after at least one prior line of chemotherapy, with 13.5% of patients demonstrating a clinical response (one complete response and six partial). 61 The MITO END-2 trial compared carboplatin, paclitaxel and bevacizumab in 108 patients with advanced or recurrent EC, with chemotherapy alone.…”

Section: P53abn Endometrial Cancermentioning

confidence: 99%

The emerging role of molecular pathology in directing the systemic treatment of endometrial cancer

2021

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Following the discovery of the four molecular subtypes of endometrial cancer (EC) by The Cancer Genome Atlas (TCGA) in 2013, subsequent studies used surrogate markers to develop and validate a clinically relevant EC classification tool to recapitulate TCGA subtypes. Molecular classification combines focused sequencing ( POLE) and immunohistochemistry (mismatch repair and p53 proteins) to assign patients with EC to one of four molecular subtypes: POLEmut, MMRd, p53abn and NSMP (no specific molecular profile). Unlike histopathological evaluation, the molecular subtyping of EC offers an objective and reproducible classification system that has been shown to have prognostic value and therapeutic implications. It is an exciting time in EC care where we have moved beyond treatment based on histomorphology alone, and molecular classification will now finally allow assessment of treatment efficacy within biologically similar tumours. It is now recommended that molecular classification should be considered for all ECs, and should be performed routinely in all high grade tumours. It is also recommended to incorporate molecular classification into standard pathology reporting and treatment decision-making algorithms. In this review, we will discuss how the molecular classification of EC can be used to guide both conventional and targeted therapy in this new molecular era.

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Angiogenesis in endometrial carcinoma: Therapies and biomarkers, current options, and future perspectives

Cited by 24 publications

References 45 publications

The Role of miRNAs in the Regulation of Endometrial Cancer Invasiveness and Metastasis—A Systematic Review

The Role of miRNAs in the Regulation of Endometrial Cancer Invasiveness and Metastasis—A Systematic Review

Fatty Acid–Binding Protein 4 (FABP4) Suppresses Proliferation and Migration of Endometrial Cancer Cells via PI3K/Akt Pathway

The emerging role of molecular pathology in directing the systemic treatment of endometrial cancer

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