Clinical cell-surface targets in metastatic and primary solid cancers.

Autor:	Sharifi MN; Department of Medicine.; Carbone Cancer Center, and., Shi Y; Department of Human Oncology, University of Wisconsin, Madison, Wisconsin, USA., Chrostek MR; Department of Human Oncology, University of Wisconsin, Madison, Wisconsin, USA., Callahan SC; Department of Human Oncology, University of Wisconsin, Madison, Wisconsin, USA., Shang T; Department of Human Oncology, University of Wisconsin, Madison, Wisconsin, USA., Berg TJ; Department of Human Oncology, University of Wisconsin, Madison, Wisconsin, USA., Helzer KT; Department of Human Oncology, University of Wisconsin, Madison, Wisconsin, USA., Bootsma ML; Department of Human Oncology, University of Wisconsin, Madison, Wisconsin, USA., Sjöström M; Department of Clinical Sciences Lund, Division of Oncology, Lund University, Lund, Sweden.; Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden., Josefsson A; Wallenberg Center for Molecular Medicine, Urology, Department of Diagnostics and Intervention, Umeå University, Umea, Sweden., Feng FY; Departments of Radiation Oncology, Urology, and Medicine, UCSF, San Francisco, California, USA., Huffman LB; Department of Obstetrics and Gynecology and., Schulte C; Department of Human Oncology, University of Wisconsin, Madison, Wisconsin, USA., Blitzer GC; Carbone Cancer Center, and.; Department of Human Oncology, University of Wisconsin, Madison, Wisconsin, USA., Sodji QH; Carbone Cancer Center, and.; Department of Human Oncology, University of Wisconsin, Madison, Wisconsin, USA., Morris ZS; Carbone Cancer Center, and.; Department of Human Oncology, University of Wisconsin, Madison, Wisconsin, USA., Ma VT; Department of Medicine.; Carbone Cancer Center, and., Meimetis L; Carbone Cancer Center, and.; Department of Radiology, University of Wisconsin, Madison, Wisconsin, USA., Kosoff D; Department of Medicine.; Carbone Cancer Center, and.; William S. Middleton Memorial Veterans' Hospital, Madison, Wisconsin, USA., Taylor AK; Department of Medicine.; Carbone Cancer Center, and., LeBeau AM; Carbone Cancer Center, and.; Department of Radiology, University of Wisconsin, Madison, Wisconsin, USA.; Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA., Lang JM; Department of Medicine.; Carbone Cancer Center, and., Zhao SG; Carbone Cancer Center, and.; Department of Human Oncology, University of Wisconsin, Madison, Wisconsin, USA.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2024 Sep 24; Vol. 9 (18). Date of Electronic Publication: 2024 Sep 24.
DOI:	10.1172/jci.insight.183674
Abstrakt:	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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu