Molecular characterization of renal cell carcinoma tumors from a phase III anti-angiogenic adjuvant therapy trial Journal Article
| Authors: | Motzer, R. J.; Martini, J. F.; Mu, X. J.; Staehler, M.; George, D. J.; Valota, O.; Lin, X.; Pandha, H. S.; Ching, K. A.; Ravaud, A. |
| Article Title: | Molecular characterization of renal cell carcinoma tumors from a phase III anti-angiogenic adjuvant therapy trial |
| Abstract: | Multigene assays can provide insight into key biological processes and prognostic information to guide development and selection of adjuvant cancer therapy. We report a comprehensive genomic and transcriptomic analysis of tumor samples from 171 patients at high risk for recurrent renal cell carcinoma post nephrectomy from the S-TRAC trial (NCT00375674). We identify gene expression signatures, including STRAC11 (derived from the sunitinib-treated population). The overlap in key elements captured in these gene expression signatures, which include genes representative of the tumor stroma microenvironment, regulatory T cell, and myeloid cells, suggests they are likely to be both prognostic and predictive of the anti-angiogenic effect in the adjuvant setting. These signatures also point to the identification of potential therapeutic targets for development in adjuvant renal cell carcinoma, such as MERTK and TDO2. Finally, our findings suggest that while anti-angiogenic adjuvant therapy might be important, it may not be sufficient to prevent recurrence and that other factors such as immune response and tumor environment may be of greater importance. © 2022, The Author(s). |
| Keywords: | survival; human tissue; treatment outcome; cancer surgery; gene mutation; human cell; major clinical study; somatic mutation; genetics; cancer recurrence; placebo; sunitinib; disease free survival; chemotherapy, adjuvant; biological marker; progression free survival; neoplasm recurrence, local; gene expression; cohort analysis; pathology; mutational analysis; transcriptomics; renal cell carcinoma; kidney neoplasms; nephrectomy; regulatory t lymphocyte; immune response; kidney tumor; carcinoma, renal cell; chromatin; tumor recurrence; adjuvant chemotherapy; molecular analysis; stroma; genomics; immunological adjuvant; phase 3 clinical trial; bone marrow cell; tumor; adjuvants, immunologic; antiangiogenic activity; immunocompetent cell; clear cell renal cell carcinoma; tumor microenvironment; elastic tissue; cell component; cancer; humans; human; article; biological processes; tumor mutational burden; protein kinase mer; c-mer tyrosine kinase |
| Journal Title: | Nature Communications |
| Volume: | 13 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2022-10-10 |
| Start Page: | 5959 |
| Language: | English |
| DOI: | 10.1038/s41467-022-33555-8 |
| PUBMED: | 36216827 |
| PROVIDER: | scopus |
| PMCID: | PMC9550765 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2022 -- Source: Scopus |
