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.
Nature communications. 2022 Oct 10*** epublish ***
Robert J Motzer, Jean-François Martini, Xinmeng J Mu, Michael Staehler, Daniel J George, Olga Valota, Xun Lin, Hardev S Pandha, Keith A Ching, Alain Ravaud
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. ., Global Product Development-Oncology, Pfizer Inc, La Jolla, CA, 92121, USA., Oncology Research Unit, Pfizer Worldwide Research and Development Medicine, Pfizer Inc, La Jolla, CA, 92121, USA., Department of Urology, University Hospital of Munich, Munich, Bavaria, 80333, Germany., Department of Medicine, Duke Cancer Institute, Durham, NC, 27710, USA., Global Product Development-Oncology, Pfizer S.r.L, Milan, Lombardy, 20152, Italy., Department of Medical Oncology, University of Surrey, Guildford, England, GU2 7XS, UK., Department of Medical Oncology, Bordeaux University Hospital, Bordeaux, 33300, France.