Molecular characterization of renal cell carcinoma tumors from a phase III anti-angiogenic adjuvant therapy trial

Robert J. Motzer (), Jean-François Martini, Xinmeng J. Mu, Michael Staehler, Daniel J. George, Olga Valota, Xun Lin, Hardev S. Pandha, Keith A. Ching and Alain Ravaud
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Robert J. Motzer: Memorial Sloan Kettering Cancer Center
Jean-François Martini: Global Product Development-Oncology, Pfizer Inc
Xinmeng J. Mu: Oncology Research Unit, Pfizer Worldwide Research and Development Medicine, Pfizer Inc
Michael Staehler: University Hospital of Munich
Daniel J. George: Duke Cancer Institute
Olga Valota: Global Product Development-Oncology, Pfizer S.r.L
Xun Lin: Global Product Development-Oncology, Pfizer Inc
Hardev S. Pandha: University of Surrey
Keith A. Ching: Oncology Research Unit, Pfizer Worldwide Research and Development Medicine, Pfizer Inc
Alain Ravaud: Bordeaux University Hospital

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-33555-8

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