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Updated: Jan 16, 2026
Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
Expression of antibody-drug conjugate targets in soft tissue sarcomas
F Bertucci1, P Finetti2, L Mescam3
1Aix Marseille Univ, INSERM U1068, Institut Paoli-Calmettes, CRCM, "Predictive Oncology laboratory", Label "Ligue contre le cancer", Marseille, France; Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France.
Background:
Soft tissue sarcomas (STSs) are aggressive and heterogeneous tumors with few efficient systemic therapies. Antibody-drug conjugates (ADCs) represent an emerging therapeutic option in oncology. Their efficacy is dependent on the expression of the ADC target on tumor cells. Very few data are available on ADC target expression in STSs.
Materials And Methods:
We analyzed the mRNA expression of 62 targets and 60 genes potentially involved in resistance/response to ADC in 1664 clinical primary tumors, including 476 liposarcomas (LPSs) 341 leiomyosarcomas, 330 undifferentiated pleomorphic sarcomas, 286 gastrointestinal stromal tumors, 126 synovial sarcomas, and 105 myxofibrosarcomas. Tumor expression in each type was compared with expression in 7414 normal tissue samples. To confirm the results at the protein level, we applied immunohistochemistry (IHC) to four ADC targets in another series of STS samples.
Results:
Expression profiles of ADC targets were heterogeneous across and within all STS types. All types expressed multiple ADC targets. An overexpression rate of at least 25% of samples in at least one type was observed for 41 targets. The high target overexpression rate in some STS types suggested numerous new therapeutic opportunities not currently studied in clinical trials, such as PTK7 overexpressed in 81% of LPSs. In addition, co-expression of ADC-target pairs and of targets with signatures of vulnerability to immune checkpoint inhibitors, poly (ADP-ribose) polymerase (PARP) inhibitors, and cyclin-dependent kinase (CDK)4/6 inhibitors was evidenced in the different pathological types, suggesting opportunities for testing ADC-based combinations. Finally, we showed heterogeneous expression profiles of potential ADC resistance/response genes between and within STS types. IHC confirmed the mRNA results for the four tested targets.
Conclusion:
STSs express multiple target genes relevant for ADC treatment and expression varies between and within the pathological types. This comprehensive ADC target landscape, based on the largest molecular epidemiology study in STS, should help clinicians and drug developers for further evaluation of ADCs across STS types.
Insights
Soft tissue sarcomas (STSs) show diverse expression of antibody-drug conjugate (ADC) targets, revealing new therapeutic avenues. This study maps the ADC target landscape in STSs, guiding future treatment strategies.
Area of Science:
- Oncology
- Molecular Epidemiology
- Pharmacogenomics
Background:
- Soft tissue sarcomas (STSs) are aggressive cancers with limited systemic treatment options.
- Antibody-drug conjugates (ADCs) offer a promising therapeutic strategy, but their effectiveness relies on target expression on tumor cells.
- Data on ADC target expression in STSs are scarce.
Purpose of the Study:
- To comprehensively analyze the expression of ADC targets and related genes in various STS subtypes.
- To identify potential new therapeutic targets and combination strategies for STS treatment.
- To provide a molecular epidemiology-based landscape of ADC targets in STSs.
Main Methods:
- mRNA expression analysis of 62 ADC targets and 60 resistance/response genes in 1664 STS samples across multiple subtypes.
- Comparison of tumor expression profiles with 7414 normal tissue samples.
- Immunohistochemistry (IHC) validation of four ADC targets at the protein level.
Main Results:
- Heterogeneous expression of ADC targets was observed across and within STS subtypes, with 41 targets overexpressed in at least 25% of samples in certain types.
- High overexpression rates for specific targets, like PTK7 in liposarcomas (81%), suggest novel therapeutic opportunities.
- Co-expression patterns indicated potential for combination therapies with immune checkpoint inhibitors, PARP inhibitors, and CDK4/6 inhibitors.
Conclusions:
- STSs exhibit diverse expression of multiple ADC target genes, varying significantly between and within pathological types.
- This extensive molecular epidemiology study establishes a crucial ADC target landscape for STSs.
- Findings will aid clinicians and drug developers in advancing ADC evaluation and treatment strategies for STS patients.
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