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Overview

 
 
HEROES-AYA is divided into six complementary and synergistic subprojects that build on the existing infrastructure of the INFORM and MASTER precision oncology programs and involve sarcoma patients and their families as well as the German Sarcoma Foundation.
The project aims to gain a better understanding of tumor heterogeneity, particularly with regard to therapy-induced changes.

Aims

Subprojects 1-3

SP1-3 explore ITH dynamics in FDS arising in adolescents and young adults (AYAs) through advanced tissue- and blood-based multi-omics, digital pathology, and imaging techniques such as radiomics. This generates an unprecedented view of ITH, capturing clonal evolution under selective pressure in cancers that posed significant clinical challenges and accounts for a third of the INFORM and MASTER patients. These cancers, with truncal genetic drivers, provide a foundation for studying ITH and evolution principles.
Subproject 1 Subproject 2 Subproject 3

Subproject 4

Subproject 4 identifies key genetic, epigenetic, transcriptomic, proteomic, histologic, and radiomorphologic events driving FDS and their tumor microenvironment (TME) using integrated data pipelines. All molecular data are made available via the German Human Genome-Phenome Archive (GHGA; https://ghga.dkfz.de) and incorporated into the Human Cell Atlas (HCA; https://www.humancellatlas.org). 
Subproject 4

Subproject 5

Subproject 5 develops in vitro and in vivo models from patient samples, reflecting FDS heterogeneity and aiding in identifying targetable dependencies via drug and genetic screens. It also models ITH-related molecular alterations in cellular systems and genetically engineered mice to explore vulnerabilities through pharmacologic and genetic screens.

Subproject 6

Subproject 6 establishs a framework for joint clinical trials in AYAs, addressing regulatory constraints, and develops a proof-of-concept protocol leveraging predictive markers and therapeutic targets identified in SP1-5 to overcome treatment resistance and improve patient outcomes.
Subproject 6