Recent Advances in the Mechanism Research and Clinical Treatment of Anti-Angiogenesis in Biliary Tract Cancer

Wang, Yue; Chen, Tianli; Li, Kangshuai; Mu, Wentao; Liu, Zengli; Shi, Anda; Li, Jialiang; Zhao, Weihua; Lian, Shuo; Huang, Shao Mei; Pan, Chang; Zhang, Zongli

doi:10.3389/fonc.2021.777617

Cited by 7 publications

(10 citation statements)

References 121 publications

(128 reference statements)

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“…Different studies have demonstrated that MVD is a hallmark of tumor neovascularization, and higher MVD is associated with an advanced tumor stage and low cure and high recurrence rates after surgical resection. Several signal cascades, including those regulated by VEGF, Platelet-derived growth factor (PDGF), and FGFR, play a crucial role in the pathogenesis and progression of BTCs [ 44 ]. Specifically, VEGF overexpression is observed in 42–76% of patients with unresectable advanced BTC and is associated with poor prognosis [ 14 , 45 ].…”

Section: Angiogenesis As a Hallmark Of Btcsmentioning

confidence: 99%

“…Furthermore, FGFR plays an important role in the regulation of cell proliferation, migration, invasion, and angiogenesis in BTC. Previous studies have identified FGFR fusions in patients with BTC and have shown that the presence of these alterations predicts a more favorable prognosis [ 44 ]. Several clinical trials of drugs targeting FGFR fusions, including Infigratinib, Pemigatinib, and Derazantinib, have been conducted [ 58 ].…”

Section: Angiogenesis As a Hallmark Of Btcsmentioning

confidence: 99%

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Targeting Angiogenesis in the Era of Biliary Tract Cancer Immunotherapy: Biological Rationale, Clinical Implications, and Future Research Avenues

Schirizzi

Leonardis

Lorusso

et al. 2023

Cancers

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Although biliary tract cancers are traditionally considered rare in Western countries, their incidence and mortality rates are rising worldwide. A better knowledge of the genomic landscape of these tumor types has broadened the number of molecular targeted therapies, including angiogenesis inhibitors. The role of immune checkpoint inhibitors (ICIs) could potentially change the first-line therapeutic approach, but monotherapy with ICIs has shown disappointing results in CCA. Several clinical trials are evaluating combination strategies that include immunotherapy together with other anticancer agents with a synergistic activity. The tumor microenvironment (TME) composition plays a pivotal role in the prognosis of BTC patients. The accumulation of immunosuppressive cell types, such as tumor-associated macrophages (TAMs) and regulatory T-cells, together with the poor infiltration of cytotoxic CD8+ T-cells, is known to predispose to a poor prognosis owing to the establishment of resistance mechanisms. Likewise, angiogenesis is recognized as a major player in modulating the TME in an immunosuppressive manner. This is the mechanistic rationale for combination treatment schemes blocking both immunity and angiogenesis. In this scenario, this review aims to provide an overview of the most recent completed or ongoing clinical trials combining immunotherapy and angiogenesis inhibitors with/without a chemotherapy backbone.

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Section: Angiogenesis As a Hallmark Of Btcsmentioning

confidence: 99%

Section: Angiogenesis As a Hallmark Of Btcsmentioning

confidence: 99%

Targeting Angiogenesis in the Era of Biliary Tract Cancer Immunotherapy: Biological Rationale, Clinical Implications, and Future Research Avenues

Schirizzi

Leonardis

Lorusso

et al. 2023

Cancers

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“…Angiogenesis plays a crucial role in the development of ESCC, by delivering oxygen and nutrients to tumors, and its key mediator is VEGF ( 138 ). Distant vascular metastasis is another way of tumor progression.…”

Section: Targeting Tumor Microenvironment For Esophageal Squamous Cel...mentioning

confidence: 99%

The Role of Tumor Microenvironment in Invasion and Metastasis of Esophageal Squamous Cell Carcinoma

2022

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Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in the world, with a high rate of morbidity. The invasion and metastasis of ESCC is the main reason for high mortality. More and more evidence suggests that metastasized cancer cells require cellular elements that contribute to ESCC tumor microenvironment (TME) formation. TME contains many immune cells and stromal components, which are critical to epithelial–mesenchymal transition, immune escape, angiogenesis/lymphangiogenesis, metastasis niche formation, and invasion/metastasis. In this review, we will focus on the mechanism of different microenvironment cellular elements in ESCC invasion and metastasis and discuss recent therapeutic attempts to restore the tumor-suppressing function of cells within the TME. It will represent the whole picture of TME in the metastasis and invasion process of ESCC.

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“…CCA, a type of bile duct cancer, is classified into two main subtypes based on its anatomical location: intrahepatic CCA (iCCA) and extrahepatic CCA (eCCA). The eCCA subtype can be further divided into perihilar CCA (pCCA) and distal CCA (dCCA) based on its specific location within the bile ducts 4–6 . CCA differs from other malignant hepatobiliary tumours as CCA contains more genomics variations 7 .…”

Section: Introductionmentioning

confidence: 99%

“…KRAS, TP53, IDH1/2 and ARID1A are the most common mutated genes in iCCA 8 while KRAS, TP53, ARID1A and SMAD4 are the most common mutated genes in eCCA 9 . despite the presence of numerous actionable genomic alterations in CCA, only a limited number of established treatment regimens are available for this disease 5,7 . For advanced CCA, the first‐line treatment is gemcitabine‐based chemotherapy, while for patients with FGFR fusion mutation, the optional treatment scheme includes pemigatinib and infigratinib 10–12 .…”

Section: Introductionmentioning

confidence: 99%

SMAD4 regulates the progression of cholangiocarcinoma by modulating the expression of STING1

Shi,

Zhao,

Sheng

et al. 2023

J Cellular Molecular Medi

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SMAD4 is a tumour suppressor and an important regulator of tumour immune scape which is downregulated in cholangiocarcinoma (CCA). STING1 is a vital sensing factor of abnormal DNA; however, the correlation between SMAD4 and STING1 and the role of the SMAD4‐STING1 interaction in the progression of CCA have not yet been evaluated. Public database was analysed to reveal the expression of SMAD4 and STING1. A cohort comprising 50 iCCA, 113 pCCA and 119 dCCA patients was assembled for the study. Immunohistochemistry was employed to evaluate the expression levels of STING1 and SMAD4. In vitro transwell and CCK8 assays, along with luciferase reporter assay, were conducted to analyse the potential regulatory mechanisms of SMAD4 on the expression of STING1. Expression of SMAD4 and STING1 were downregulated in CCA tumours and STING1 expression correlated with SMAD4 expression. The overexpression of SMAD4 was found to suppress the migration, invasion and proliferation capabilities of CCA cells; whereas, the knockdown of SMAD4 enhanced these abilities. Furthermore, it was observed that SMAD4 translocated into the nucleus following TGF‐β1 stimulation. Knockdown of SMAD4 resulted in the inhibition of STING1 transcriptional activity, whereas the overexpression of SMAD4 promoted the transcriptional activity of STING1. Clinically, low STING1 and SMAD4 expression indicated poor prognosis in CCA, and simultaneously low expression of STING1 and SMAD4 predicts poorer patient survival. SMAD4 regulates the expression of STING1 through its transcription regulating function. Dual low expression of STING1 and SMAD4 had more power in predicting patient survival. These results indicate that SMAD4‐silenced CCA may downregulate its STING1 expression to adapt to the immune system.

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Recent Advances in the Mechanism Research and Clinical Treatment of Anti-Angiogenesis in Biliary Tract Cancer

Cited by 7 publications

References 121 publications

Targeting Angiogenesis in the Era of Biliary Tract Cancer Immunotherapy: Biological Rationale, Clinical Implications, and Future Research Avenues

Targeting Angiogenesis in the Era of Biliary Tract Cancer Immunotherapy: Biological Rationale, Clinical Implications, and Future Research Avenues

The Role of Tumor Microenvironment in Invasion and Metastasis of Esophageal Squamous Cell Carcinoma

SMAD4 regulates the progression of cholangiocarcinoma by modulating the expression of STING1

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