Expanding individualized therapeutic options via genoproteomics.

Cancer Lett

KingMed-Pineal Joint Innovation Laboratory of Clinical Proteomics, Guangzhou KingMed Center for Clinical Laboratory Co., Ltd., Guangzhou, 510009, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, 102206, China; State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Fudan University, Shanghai, 200433, China. Electronic address:

Published: April 2023

Clinical next-generation sequencing (NGS) tests have enabled treatment recommendations for cancer patients with driver gene mutations. Targeted therapy options for patients without driver gene mutations are currently unavailable. Herein, we performed NGS and proteomics tests on 169 formalin-fixed paraffin-embedded (FFPE) samples of non-small cell lung cancers (NSCLC, 65), colorectal cancers (CRC, 61), thyroid carcinomas (THCA, 14), gastric cancers (GC, 2), gastrointestinal stromal tumors (GIST, 11), and malignant melanomas (MM, 6). Of the 169 samples, NGS detected 14 actionable mutated genes in 73 samples, providing treatment options for 43% of the patients. Proteomics identified 61 actionable clinical drug targets approved by the FDA or undergoing clinical trials in 122 samples, providing treatment options for 72% of the patients. In vivo experiments demonstrated that the Mitogen-Activated Protein Kinase (MEK) inhibitor could block lung tumor growth in mice with overexpression of Map2k1 protein. Therefore, protein overexpression is a potentially feasible indicator for guiding targeted therapies. Collectively, our analysis suggests that combining NGS and proteomics (genoproteomics) could expand the targeted treatment options to 85% of cancer patients.

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Source
http://dx.doi.org/10.1016/j.canlet.2023.216123DOI Listing

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