Current Model Systems for Investigating Epithelioid Haemangioendothelioma

SIMPLE SUMMARY: Epithelioid haemangioendothelioma is a rare type of cancer with an unpredictable disease course and very few treatment options. To better understand how this type of cancer develops and to uncover possible lines of treatment, it is critical to have experimental approaches to study this cancer. Here, we describe and compare the model systems that are currently available to study this disease. The research undertaken and the discoveries made using each of these experimental models is presented, and the advantages and disadvantages of each model are discussed. ABSTRACT: Epithelioid haemangioendothelioma (EHE) is a rare sarcoma of the vascular endothelium with an unpredictable disease course. EHE tumours can remain indolent for long period of time but may suddenly evolve into an aggressive disease with widespread metastases and a poor prognosis. Two mutually exclusive chromosomal translocations define EHE tumours, each involving one of the transcription co-factors TAZ and YAP. The TAZ-CAMTA1 fusion protein results from a t(1;3) translocation and is present in 90% of EHE tumours. The remaining 10% of EHE cases harbour a t(X;11) translocation, resulting in the YAP1-TFE3 (YT) fusion protein. Until recently, the lack of representative EHE models made it challenging to study the mechanisms by which these fusion proteins promote tumorigenesis. Here, we describe and compare the recently developed experimental approaches that are currently available for studying this cancer. After summarising the key findings obtained with each experimental approach, we discuss the advantages and limitations of these different model systems. Our survey of the current literature shows how each experimental approach can be utilised in different ways to improve our understanding of EHE initiation and progression. Ultimately, this should lead to better treatment options for patients.