Translational aspects of epithelioid sarcoma: Current consensus Review
| Authors: | Grünewald, T. G. P.; Postel-Vinay, S.; Nakayama, R. T.; Berlow, N. E.; Bolzicco, A.; Cerullo, V.; Dermawan, J. K.; Frezza, A. M.; Italiano, A.; Jin, J. X.; Le Loarer, F.; Martin-Broto, J.; Pecora, A.; Perez-Martinez, A.; Tam, Y. B.; Tirode, F.; Trama, A.; Pasquali, S.; Vescia, M.; Wortmann, L.; Wortmann, M.; Yoshida, A.; Webb, K.; Huang, P. H.; Keller, C.; Antonescu, C. R. |
| Review Title: | Translational aspects of epithelioid sarcoma: Current consensus |
| 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. © 2024 American Association for Cancer Research Inc.. All rights reserved. |
| Keywords: | adolescent; cancer chemotherapy; protein expression; young adult; unclassified drug; dna binding protein; gene mutation; gene deletion; genetics; dna-binding proteins; sequence deletion; review; doxorubicin; liver cell carcinoma; solid tumor; sensitivity analysis; colorectal cancer; nonhistone protein; metabolism; chromosomal proteins, non-histone; ipilimumab; consensus; gene expression; protein; transcription factor; angiosarcoma; proteomics; bladder cancer; dna methylation; transcription factors; sarcoma; immunotherapy; kidney tumor; neuroblastoma; irradiation; homozygote; soft tissue sarcoma; genomics; pancreas adenocarcinoma; bile duct carcinoma; synovial sarcoma; chordoma; epithelioid sarcoma; translational research; desmoplastic small round cell tumor; non small cell lung cancer; molecular pathology; molecular diagnosis; beta actin; demographics; epithelioid hemangioendothelioma; fusidic acid; nivolumab; talimogene laherparepvec; humans; human; smarcb1 protein; rna sequencing; pembrolizumab; durvalumab; atezolizumab; tazemetostat; congenital tumor; malignant neoplasm; endometrial clear cell carcinoma; swi/snf related matrix associated actin dependent regulator of chromatin subfamily b member 1; thoracic cancer; b cell cll lymphoma 7 protein family member c; thoracic tumor; ovarian clear cell adenocarcinoma; tiragolumab; neurofibromatosis type 3; b cell cll lymphoma 7 protein family member a; b cell cll lymphoma 7 protein family member b; brg1 associated factor 155; brg1 associated factor 170; brg1 associated factor 180; brg1 associated factor 200; brg1 associated factor 250a; brg1 associated factor 250b; brg1 associated factor 45a; brg1 associated factor 45b; brg1 associated factor 45c; brg1 associated factor 45d; brg1 associated factor 53a; brg1 associated factor 53b; brg1 associated factor 57; brg1 associated factor 60a; brg1 associated factor 60b; brg1 associated factor 6b; brg1 associated factor c; bromodomain containing 7; bromodomain containing 9; synovial sarcoma translocation chromosome 18; synovial sarcoma translocation chromosome l1; current consensus |
| Journal Title: | Clinical Cancer Research |
| Volume: | 30 |
| Issue: | 6 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2024-03-15 |
| Start Page: | 1079 |
| End Page: | 1092 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-23-2174 |
| PUBMED: | 37916971 |
| PROVIDER: | scopus |
| PMCID: | PMC10947972 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Cristina R. Antonescu -- Source: Scopus |
