Translational Aspects of Epithelioid Sarcoma: Current Consensus
Thomas G.P. Grünewald
(1, 2, 3, 4)
,
Sophie Postel-Vinay
(5, 6)
,
Robert Nakayama
(7)
,
Noah Berlow
(8)
,
Andrea Bolzicco
(9, 10)
,
Vincenzo Cerullo
(11)
,
Josephine Dermawan
(12)
,
Anna Maria Frezza
(13)
,
Antoine Italiano
(14, 15)
,
Jia Xiang Jin
(1, 2)
,
Francois Le Loarer
(14, 15)
,
Javier Martin-Broto
(16, 17, 18)
,
Andrew Pecora
(19)
,
Antonio Perez-Martinez
(20, 21, 22)
,
Yuen Bun Tam
(23)
,
Franck Tirode
(24, 25)
,
Annalisa Trama
(26)
,
Sandro Pasquali
(26)
,
Mariagrazia Vescia
(10)
,
Lukas Wortmann
(27)
,
Michael Wortmann
(27)
,
Akihiko Yoshida
(28)
,
Kim Webb
(27)
,
Paul Huang
(23, 29)
,
Charles Keller
(8)
,
Cristina Antonescu
(30)
1
DKFZ -
German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg]
2 KITZ - Hopp Children's Cancer Center Heidelberg [Heidelber, Germany]
3 Heidelberg University Hospital [Heidelberg]
4 NCT / DKFZ - National Center for Tumor Diseases - Deutsches Krebsforschungszentrum [Heidelberg, Allemagne]
5 IGR - Institut Gustave Roussy
6 U981 - Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse
7 Keio University [Tokyo]
8 CCTDI - Children's Cancer Therapy Development Institute [Oregon]
9 OPVA - Patients association 'Orchestra per la vita' Aps [Rome, Italy]
10 MC4 - Patients association: 'MC4 in corsa per la vita!' ETS [Milan, Italy]
11 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
12 Cleveland Clinic
13 Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan]
14 Institut Bergonié [Bordeaux]
15 UB - Université de Bordeaux
16 FJD - Fundacion Jimenez Diaz [Madrid]
17 General Hospital of Villalba [Madrid]
18 IIS-FJD - Instituto de Investigación Sanitaria Fundación Jiménez Diaz [Madrid]
19 Georgetown Lombardi Comprehensive Cancer Center
20 UAM - Universidad Autónoma de Madrid
21 IdiPAZ - Instituto de Investigación La Paz [Madrid, Spain]
22 La Paz University Hospital
23 The institute of cancer research [London]
24 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
25 Centre Léon Bérard [Lyon]
26 IRCCS Istituto Nazionale dei Tumori [Milano]
27 SMARCB - Patients association "Smarcb1" [Bergisch Gladbach, Germany]
28 National Cancer Institute Central Hospital [Tokyo, Japan]
29 Royal Marsden Hospital [Surrey, UK]
30 MSKCC - Memorial Sloan Kettering Cancer Center
2 KITZ - Hopp Children's Cancer Center Heidelberg [Heidelber, Germany]
3 Heidelberg University Hospital [Heidelberg]
4 NCT / DKFZ - National Center for Tumor Diseases - Deutsches Krebsforschungszentrum [Heidelberg, Allemagne]
5 IGR - Institut Gustave Roussy
6 U981 - Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse
7 Keio University [Tokyo]
8 CCTDI - Children's Cancer Therapy Development Institute [Oregon]
9 OPVA - Patients association 'Orchestra per la vita' Aps [Rome, Italy]
10 MC4 - Patients association: 'MC4 in corsa per la vita!' ETS [Milan, Italy]
11 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
12 Cleveland Clinic
13 Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan]
14 Institut Bergonié [Bordeaux]
15 UB - Université de Bordeaux
16 FJD - Fundacion Jimenez Diaz [Madrid]
17 General Hospital of Villalba [Madrid]
18 IIS-FJD - Instituto de Investigación Sanitaria Fundación Jiménez Diaz [Madrid]
19 Georgetown Lombardi Comprehensive Cancer Center
20 UAM - Universidad Autónoma de Madrid
21 IdiPAZ - Instituto de Investigación La Paz [Madrid, Spain]
22 La Paz University Hospital
23 The institute of cancer research [London]
24 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
25 Centre Léon Bérard [Lyon]
26 IRCCS Istituto Nazionale dei Tumori [Milano]
27 SMARCB - Patients association "Smarcb1" [Bergisch Gladbach, Germany]
28 National Cancer Institute Central Hospital [Tokyo, Japan]
29 Royal Marsden Hospital [Surrey, UK]
30 MSKCC - Memorial Sloan Kettering Cancer Center
Thomas G.P. Grünewald
- Fonction : Auteur
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Sophie Postel-Vinay
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Robert Nakayama
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Noah Berlow
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- ORCID : 0000-0001-8666-3152
Andrea Bolzicco
- Fonction : Auteur
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Vincenzo Cerullo
- Fonction : Auteur
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Josephine Dermawan
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Anna Maria Frezza
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- ORCID : 0000-0003-2335-7224
Antoine Italiano
- Fonction : Auteur
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- ORCID : 0000-0002-8540-5351
Jia Xiang Jin
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Francois Le Loarer
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Javier Martin-Broto
- Fonction : Auteur
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- ORCID : 0000-0001-7350-6916
Andrew Pecora
- Fonction : Auteur
- PersonId : 1366676
- ORCID : 0009-0001-8034-932X
Antonio Perez-Martinez
- Fonction : Auteur
- PersonId : 1366677
- ORCID : 0000-0002-6436-9195
Yuen Bun Tam
- Fonction : Auteur
- PersonId : 1366678
- ORCID : 0000-0002-1319-5148
Franck Tirode
- Fonction : Auteur
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- IdHAL : franck-tirode
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Annalisa Trama
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- ORCID : 0000-0001-8220-9833
Sandro Pasquali
- Fonction : Auteur
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- ORCID : 0000-0003-4815-6293
Mariagrazia Vescia
- Fonction : Auteur
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- ORCID : 0009-0002-6984-8029
Lukas Wortmann
- Fonction : Auteur
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- ORCID : 0009-0003-0717-8979
Michael Wortmann
- Fonction : Auteur
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- ORCID : 0009-0006-3386-4333
Akihiko Yoshida
- Fonction : Auteur
- PersonId : 1366683
- ORCID : 0000-0002-3373-0099
Kim Webb
- Fonction : Auteur
- PersonId : 1366684
- ORCID : 0009-0001-7011-2193
Paul Huang
- Fonction : Auteur
- PersonId : 1366685
- ORCID : 0000-0003-3972-5087
Charles Keller
- Fonction : Auteur
- PersonId : 1366686
- ORCID : 0000-0003-2505-7487
Cristina Antonescu
- Fonction : Auteur
- PersonId : 1366687
- ORCID : 0000-0002-9717-8205
Résumé
Abstract Epithelioid sarcoma (EpS) is an ultra-rare malignant soft-tissue cancer mostly affecting adolescents and young adults. EpS often exhibits an unfavorable clinical course with fatal outcome in ∼50% of cases despite aggressive multimodal therapies combining surgery, chemotherapy, and irradiation. EpS is traditionally classified in a more common, less aggressive distal (classic) type and a rarer aggressive proximal type. Both subtypes are characterized by a loss of nuclear INI1 expression, most often following homozygous deletion of its encoding gene, SMARCB1—a core subunit of the SWI/SNF chromatin remodeling complex. In 2020, the EZH2 inhibitor tazemetostat was the first targeted therapy approved for EpS, raising new hopes. Still, the vast majority of patients did not benefit from this drug or relapsed rapidly. Further, other recent therapeutic modalities, including immunotherapy, are only effective in a fraction of patients. Thus, novel strategies, specifically targeted to EpS, are urgently needed. To accelerate translational research on EpS and eventually boost the discovery and development of new diagnostic tools and therapeutic options, a vibrant translational research community has formed in past years and held two international EpS digital expert meetings in 2021 and 2023. This review summarizes our current understanding of EpS from the translational research perspective and points to innovative research directions to address the most pressing questions in the field, as defined by expert consensus and patient advocacy groups.