Shifting from a Biological-Agnostic Approach to a Molecular-Driven Strategy in Rare Cancers - Ewing Sarcoma Archetype

Sep 28, 2026

Uploaded by Patrick

Sarcomas of the thoracic cavity are rare and affect mostly children and young adults, showing substantial histological heterogeneity. Ewing sarcoma (ES) can arise in many bone, soft-tissue, or visceral sites, yet thoracic involvement is exceedingly uncommon and represents the second most frequent thoracic sarcoma after chondrosarcoma. Standard management is multidisciplinary (surgery, radiotherapy, systemic therapy) but long-term outcomes remain poor. Owing to limited trials, no optimal recurrence strategy exists, motivating reviews of molecular mechanisms and current preclinical and clinical therapeutic advances.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages27

Reading Time1 h 8 min

AccessFree to download

Introduction

Molecular basis and diagnosis

Treatment landscape and future directions

biomedicines Review Shifting from a Biological-Agnostic Approach to a Molecular-Driven Strategy in Rare Cancers: Ewing Sarcoma Archetype Aldo Caltavituro 1,†, Roberto Buonaiuto 1,†, Erica Pietroluongo 1, Rocco Morra 1, Fabio Salomone 1, Pietro De Placido 1, Martina Pagliuca 2,3, Angelo Vaia 4, Margaret Ottaviano 5,6, Marianna Tortora 6, Sabino De Placido 1,6, Giovannella Palmieri 6 and Mario Giuliano 1,6, * Citation: Caltavituro, A.; Buonaiuto, R.; Pietroluongo, E.; Morra, R.; Salomone, F.; De Placido, P.; Pagliuca, M.; Vaia, A.; Ottaviano, M.; Tortora, M.; et al. Shifting from a Biological-Agnostic Approach to a Molecular-Driven Strategy in Rare Cancers: Ewing Sarcoma Archetype. Biomedicines 2023, 11, 874 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)biomedicines11030874 Academic Editor: Paola Maroni Received: 2 January 2023 Revised: 24 February 2023 Accepted: 8 March 2023 Published: 13 March 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy 2 Scuola Superiore Meridionale (SSM), Clinical and Translational Oncology, 80138 Naples, Italy 3 Gustave Roussy, 94805 Villejuif, France 4 Medical Oncology Unit,“San Carlo” Hospital, 85100 Napoli, Italy 5 Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Campania, 80131 Napoli, Italy 6 CRCTR Coordinating Rare Tumors Reference Center of Campania Region, 80131 Naples, Italy * [Correspondence: m.giuliano@unina.it](Correspondence: m.giuliano@unina.it)[ ](Correspondence: m.giuliano@unina.it)† These authors contributed equally to this work. Abstract: Sarcomas of the thoracic cavity are rare entities that predominantly affect children and young adults. They can be very heterogeneous encompassing several different histological entities. Ewing Sarcoma (ES) can potentially arise from every bone, soft tissue, or visceral site in the body. However, it represents an extremely rare ﬁnding when it affects the thoracic cavity. It represents the second most frequent type of thoracic sarcoma, after chondrosarcoma. ES arises more frequently in sites that differ from the thoracic cavity, but it displays the same biological features and behavior of extra-thoracic ones. Current management of ES often requires a multidisciplinary treatment approach including surgery, radiotherapy, and systemic therapy, as it can guarantee local and distant disease control, at least transiently, although the long-term outcome remains poor. Unfortunately, due to the paucity of clinical trials purposely designed for this rare malignancy, there are no optimal strategies that can be used for disease recurrence. As a result of its complex biological features, ES might be suitable for emerging biology-based therapeutic strategies. However, a deeper understanding of the molecular mechanisms driving tumor growth and treatment resistance, including those related tooncogenic pathways, epigenetic landscape, and immune microenvironment, is necessary in order to develop new valid therapeutic opportunities. Here, we provide an overview of the most recent therapeutic advances for ES in both the preclinical and clinical settings. We performed a review of the current available literature and of the ongoing clinical trials focusing on new treatment strategies, after failure of conventional multimodal treatments. Keywords: ewing sarcoma; rare thoracic tumors; epigenetics; immunotherapy; biology 1. Introduction Ewing's sarcoma (ES) is an extremely rare malignancy with an incidence of one case

FAQs

Why is Ewing sarcoma in the thoracic cavity considered rare?

Thoracic cavity ES is an extremely rare finding despite ES being able to arise from many bone, soft-tissue, or visceral sites. It represents the second most frequent type of thoracic sarcoma after chondrosarcoma.

What is the key molecular event in most Ewing sarcoma cases?

Most cases involve the t(11;22) translocation generating the EWSR1-FLI1 fusion gene. A smaller fraction involves EWSR1 fused with ERG via t(21;22).

What limits current management of Ewing sarcoma recurrence?

The paucity of clinical trials specifically designed for this rare malignancy means there are no optimal strategies for disease recurrence, even though multidisciplinary treatment can provide transient local and distant control.

Sep 28, 2026

Uploaded by Patrick