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Clinical cell-surface targets in metastatic and primary solid cancers

Sharifi, Marina N. ; Shi, Yue ; Chrostek, Matthew R. ; Carson Callahan, S. ; Shang, Tianfu ; Berg, Tracy J. LU ; Helzer, Kyle T. ; Bootsma, Matthew L. ; Sjöström, Martin LU and Josefsson, Andreas , et al. (2024) In JCI Insight 9(18).
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
JCI Insight
volume
9
issue
18
article number
e183674
publisher
The American Society for Clinical Investigation
external identifiers
  • pmid:39315546
  • scopus:85204790102
ISSN
2379-3708
DOI
10.1172/jci.insight.183674
language
English
LU publication?
yes
id
3d55affc-5dbb-4bc9-862c-b387f470f53c
date added to LUP
2024-11-22 15:23:37
date last changed
2025-07-05 10:59:35
@article{3d55affc-5dbb-4bc9-862c-b387f470f53c,
  abstract     = {{<p>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.</p>}},
  author       = {{Sharifi, Marina N. and Shi, Yue and Chrostek, Matthew R. and Carson Callahan, S. and Shang, Tianfu and Berg, Tracy J. and Helzer, Kyle T. and Bootsma, Matthew L. and Sjöström, Martin and Josefsson, Andreas and Feng, Felix Y. and Huffman, Laura B. and Schulte, Chris and Blitzer, Grace C. and Sodji, Quaovi H. and Morris, Zachary S. and Ma, Vincent T. and Meimetis, Labros and Kosoff, David and Taylor, Amy K. and LeBeau, Aaron M. and Lang, Joshua M. and Zhao, Shuang G.}},
  issn         = {{2379-3708}},
  language     = {{eng}},
  number       = {{18}},
  publisher    = {{The American Society for Clinical Investigation}},
  series       = {{JCI Insight}},
  title        = {{Clinical cell-surface targets in metastatic and primary solid cancers}},
  url          = {{http://dx.doi.org/10.1172/jci.insight.183674}},
  doi          = {{10.1172/jci.insight.183674}},
  volume       = {{9}},
  year         = {{2024}},
}