VEGF-VEGFR pathway seems to be the best target in hepatic epithelioid hemangioendothelioma: A case series with review of the literature

Telli, Tuğba Akın; Ökten, İlker; Tüylü, Tuğba Başoğlu; Demircan, Nazım Can; Arıkan, Rukiye; Alan, Özkan; Ercelep, Özlem; Öneş, Tunç; Yildirim, Aysenur Toksoz; Dane, Faysal; Yumuk, Perran Fulden

doi:10.1016/j.currproblcancer.2020.100568

Cited by 6 publications

(8 citation statements)

References 37 publications

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“…Interestingly, drugs targeting several of these processes have already shown some clinical benefit. For example, we identified Vegfa to be transcriptionally up-regulated in MS1 cells expressing TAZ-CAMTA1, and VEGF inhibitors have been shown to be beneficial in patients with EHE (Telli et al 2020). Additionally, an mTOR-activated gene signature was observed in the proliferative endothelial cell population, and the mTOR inhibitor sirolimus has benefited some patients (Stacchiotti et al 2016).…”

Section: Discussionmentioning

confidence: 99%

WWTR1(TAZ)-CAMTA1 reprograms endothelial cells to drive epithelioid hemangioendothelioma

Driskill

Zheng

et al. 2021

Genes Dev.

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Epithelioid hemangioendothelioma (EHE) is a poorly understood and devastating vascular cancer. Sequencing of EHE has revealed a unique gene fusion between the Hippo pathway nuclear effector TAZ (WWTR1) and the brain-enriched transcription factor CAMTA1 in ∼90% of cases. However, it remains unclear whether the TAZ-CAMTA1 gene fusion is a driver of EHE, and potential targeted therapies are unknown. Here, we show that TAZ-CAMTA1 expression in endothelial cells is sufficient to drive the formation of vascular tumors with the distinctive features of EHE, and inhibition of TAZ-CAMTA1 results in the regression of these vascular tumors. We further show that activated TAZ resembles TAZ-CAMTA1 in driving the formation of EHE-like vascular tumors, suggesting that constitutive activation of TAZ underlies the pathological features of EHE. We show that TAZ-CAMTA1 initiates an angiogenic and regenerative-like transcriptional program in endothelial cells, and disruption of the TAZ-CAMTA1-TEAD interaction or ectopic expression of a dominant negative TEAD in vivo inhibits TAZ-CAMTA1-mediated transformation. Our study provides the first genetic model of a TAZ fusion oncoprotein driving its associated human cancer, pinpointing TAZ-CAMTA1 as the key driver and a valid therapeutic target of EHE.

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Section: Discussionmentioning

confidence: 99%

WWTR1(TAZ)-CAMTA1 reprograms endothelial cells to drive epithelioid hemangioendothelioma

Driskill

Zheng

et al. 2021

Genes Dev.

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“…The expression of nuclear CAMTA1 in approximately 85%–90% of cases is currently the main immunohistochemical diagnostic test for HEHE, which may be localized or multifocal and metastatic. 1 , 4 , 5 , 10 …”

Section: Discussionmentioning

confidence: 99%

Advanced epithelioid hemangioendothelioma of the liver: could lenvatinib offer a bridge treatment to liver transplantation?

Kounis

Lewin²,

Laurent-Bellue³

et al. 2022

Ther Adv Med Oncol

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In this article, we describe the case of a 34-year-old woman presenting a multifocal and metastatic epithelioid hemangioendothelioma (HEHE) of the liver. Under classical chemotherapy using cyclophosphamide, there was a fast tumor progression in liver and extra-hepatic metastatic sites (lungs and mediastinal lymph node). Taking into account the patient’s age and the natural history of the HEHE, our goal was to try to bring her to liver transplantation (LT) and lenvatinib was an acceptable candidate for this reason. Shortly after the initiation of lenvatinib before LT and surgery, we observed the enlargement of large devascularized necrotic areas in most of the liver HEHE masses, suggesting a good response. The patient was finally transplanted 6 months after initiation of lenvatinib treatment. Eight months after LT, progression occurred (ascites, peritoneal recurrence, and mediastinal lymph node). After restarting lenvatinib, ascites disappeared and the lymph node decreased in size, suggesting a good response, more than 1 year after her transplantation. This is the first case report to our knowledge that illustrates the benefit of lenvatinib as a neoadjuvant bridge until LT for a multifocal and metastatic HEHE. In addition, this drug has also shown a benefit in term of disease control after a late recurrence of the tumor. We suggest that lenvatinib should be proposed as a bridge to the LT for nonresectable HEHE. Moreover, this drug was also beneficial in the treatment of late recurrence after LT. The absence of pharmacologic interactions between classical immunosuppressive drugs and lenvatinib may allow its use as an early adjuvant approach when the risk of recurrence is high. The strength of our case consists in the long follow-up and the innovative message allowing changing palliative strategies into curative ones in case of advanced HEHE.

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“…The prognosis of HEHE are vary different, and early diagnosis and treatment are critical, 22 and 5‐year survival rate of only 5% 3 without treatment. However, the survival rate of patients treated with surgery was significantly higher than that of other patients (5‐year survival rate: 88% vs. 49%, P = .019) and was the only independent prognostic factor for survival (hazard ratio: 0.20, P = .040), 6 Therefore, radical surgical resection or liver transplantation is the preferred method for patients with local liver involvement, 8 However, HEHE often has multiple lesions and the lack of organ donation, surgical resection and liver transplantation are usually not feasible, 23,24 Other scholars reported that the lesions of some untreated patients were in a stable state during reexamination, 25 and some lesions even disappeared 7 . Thomas et al proposed a new strategy: Observing the clinical behavior of HEHE may be a key step in management.…”

Section: Discussionmentioning

confidence: 99%

Three cases of hepatic epithelioid hemangioendothelioma evaluated using conventional and contrast‐enhanced ultrasound: Case reports

Jian-qiang

Zhao

et al. 2022

J of Clinical Ultrasound

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Hepatic epithelioid hemangioendothelioma (HEHE) is a very rare vascular endothelial cell tumor, which lacks typical clinical manifestations and specificity of imaging features. Whether the background of fatty liver and the difference in Contrast enhanced ultrasound (CEUS) characteristics between large and small lesions has not been well defined. In this case reports, we described the ultrasound image features of three patients with HEHE. These three patients with HEHE have certain similar characteristics of conventional ultrasound and CEUS. CEUS imaging features include large nodules show earlier perfusion than liver parenchyma, with rim‐enhancement, nonenhancing regions in the center, while small nodules show earlier perfusion than liver parenchyma, with hyperenhancement. All nodules show faster washout than hepatic parenchyma, showing heterogeneous hypoenhancement, and more washout lesions can be found in the PVP and LP. Conventional ultrasound and CEUS not only help to improve the diagnostic confidence of HEHE of rare liver tumors, but also can guide the biopsy area, making it easier to make accurate pathological diagnosis.

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VEGF-VEGFR pathway seems to be the best target in hepatic epithelioid hemangioendothelioma: A case series with review of the literature

Cited by 6 publications

References 37 publications

WWTR1(TAZ)-CAMTA1 reprograms endothelial cells to drive epithelioid hemangioendothelioma

WWTR1(TAZ)-CAMTA1 reprograms endothelial cells to drive epithelioid hemangioendothelioma

Advanced epithelioid hemangioendothelioma of the liver: could lenvatinib offer a bridge treatment to liver transplantation?

Three cases of hepatic epithelioid hemangioendothelioma evaluated using conventional and contrast‐enhanced ultrasound: Case reports

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