Journal Article (Review Article)

DKFZ-2026-00345

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Intratumor Heterogeneity and Clonal Evolution in Sarcomas: Molecular, Cellular, and Functional Drivers of Therapy Resistance.

Grünewald, T. (First author)DKFZ* ; Oehme, I.DKFZ* ; Wagner, J.DKFZ* ; Fröhling, S. (Last author)DKFZ*

2026
Academic Press London

Abstract: Sarcomas, malignant neoplasms of mesenchymal origin, comprise more than 100 entities and numerous histologic subtypes. Their relative rarity compared with carcinomas, interpatient diversity, and pronounced intratumor heterogeneity (ITH) make sarcomas clinically challenging. Yet, they also provide excellent models for studying the molecular and cellular underpinnings of ITH and how it translates into diverse clinical outcomes. New single-cell and spatial omics technologies have revealed the complex architecture of sarcomas with unprecedented resolution. In this review, we use five representative entities - two genomically complex (osteosarcoma, dedifferentiated liposarcoma) and three fusion-driven, genomically 'quieter' (Ewing sarcoma, synovial sarcoma, alveolar rhabdomyosarcoma) sarcomas - to showcase recent advances in the field of ITH and the temporal evolution of sarcomas. Specifically, we review how clonal and subclonal molecular alterations, fluctuations in oncogene activity and other forms of cellular plasticity, as well as the formation of complex intratumor ecosystems, drive sarcoma progression and shape therapy resistance. We also provide an overview of recent advances in modeling ITH in sarcomas, as well as in evaluating functional diversity and assessing patient-specific treatment responses. Finally, we outline future directions in ITH research and its clinical implications.

Note: #EA:B410#LA:B340# / #DKTKZFB26# / #NCTZFB26# / epub

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Contributing Institute(s):

1. Translationale Pädiatrische Sarkomforschung (B410)
2. DKTK HD zentral (HD01)
3. KKE Pädiatrische Onkologie (B310)
4. Translationale Medizinische Onkologie (B340)
5. Koordinierungsstelle NCT Heidelberg (HD02)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2026

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Database coverage:
; BIOSIS Previews ; BIOSIS Reviews Reports And Meetings ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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