Clinical cell-surface targets in metastatic and primary solid cancers
Therapies against cell-surface targets (CSTs) represent an emerging treatment class in solid malignancies. However, high-throughput investigations of CST expression across cancer types have been reliant on data sets of mostly primary tumors, despite therapeutic use most commonly in metastatic disease. We identified a total of 818 clinical trials of CST therapies with 78 CSTs. We assembled a data set spanning RNA-seq and microarrays in 7,927 benign samples, 16,866 primary tumor samples, and 6,124 metastatic tumor samples. We also utilized single-cell RNA-seq data from 36 benign tissues and 558 primary and metastatic tumor samples, and matched RNA versus protein expression in 29 benign tissue samples, 1,075 tumor samples, and 942 cell lines. High RNA expression accurately predicted high protein expression across CST therapies in benign tissues, tumor samples, and cell lines. We compared metastatic versus primary tumor expression, identified potential opportunities for repositioning, and matched cell lines to tumor types based on CST and global RNA expression. We evaluated single-cell heterogeneity across tumors, and identified rare normal cell subpopulations that may contribute to toxicity. Finally, we identified combinations of CST therapies for which bispecific approaches could improve tumor specificity. This study helps better define the landscape of CST expression in metastatic and primary cancers.
Authors
- Quaovi H. Sodji (ORCID: https://orcid.org/0000-0002-9469-1388)
- Tracy J. Berg (ORCID: https://orcid.org/0009-0006-1560-7827)
- Joshua M. Lang (ORCID: https://orcid.org/0000-0002-0943-8872)
- Matthew R. Chrostek (ORCID: https://orcid.org/0000-0002-9457-1431)
- Felix Yi-Chung Feng (ORCID: https://orcid.org/0000-0002-0963-7687)
- Kyle T. Helzer (ORCID: https://orcid.org/0000-0003-3853-5564)
- Aaron M. LeBeau (ORCID: https://orcid.org/0000-0003-3802-7789)
- Zachary S. Morris (ORCID: https://orcid.org/0000-0001-5558-3547)
- Martin Sjöström (ORCID: https://orcid.org/0000-0002-2629-9966)
- Yue Shi (ORCID: https://orcid.org/0000-0002-2860-2666)
- Marina N. Sharifi (ORCID: https://orcid.org/0000-0003-0128-3033)
- S. Carson Callahan (ORCID: https://orcid.org/0000-0002-0152-2666)
- Grace C. Blitzer (ORCID: https://orcid.org/0000-0003-3178-3004)
- Amy K. Taylor (ORCID: https://orcid.org/0000-0003-4559-4159)
- Andreas Josefsson (ORCID: https://orcid.org/0000-0002-2013-0887)
- Timothy A. Vincent (ORCID: https://orcid.org/0000-0002-3520-6610)
- Matthew L. Bootsma (ORCID: https://orcid.org/0000-0003-0879-5066)
- Shuang George Zhao (ORCID: https://orcid.org/0000-0002-9166-6507)
- David Kosoff (ORCID: https://orcid.org/0000-0001-8559-6357)
- Labros Meimetis (ORCID: https://orcid.org/0000-0002-5304-2066)
- Laura Huffman
- Chris Schulte
- Tianfu Andy Shang
Institutions
- University of Wisconsin–Madison (US)
- University of California, San Francisco (US)
- Lund University (SE)
- University of Wisconsin Carbone Cancer Center (US)
- Skåne University Hospital (SE)
- William S. Middleton Memorial Veterans Hospital (US)
- Umeå University (SE)
Publication Details
- Journal
- JCI Insight
- Published
- 2024-09-23
- DOI
- https://doi.org/10.1172/jci.insight.183674
- Citations
- 10
- Primary Topic
- Cancer Cells and Metastasis
- Type
- article
- Field-Weighted Citation Impact
- 2.83
Funders
- U.S. Department of Defense
- Wisconsin Alumni Research Foundation
- NIH Office of the Director