Molecular Subsets in Renal Cancer Determine Outcome to Checkpoint and Angiogenesis Blockade
| Autor: | Li-Fen Liu, David F. McDermott, Jinzhen Fan, Susheela Carroll, Michael B. Atkins, Alexander R. Abbas, Ning Leng, Robert J. Motzer, Habib Hamidi, Darren Tayama, Thomas Powles, Sanjeev Mariathasan, Christina Schiff, Bernard Escudier, Hartmut Koeppen, Romain Banchereau, Mahrukh Huseni, Jennifer C Lin, Brian I. Rini, Priti Hegde, Kenji Hashimoto, Marjorie C. Green |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Bevacizumab Angiogenesis Angiogenesis Inhibitors Antibodies Monoclonal Humanized Article 03 medical and health sciences 0302 clinical medicine CDKN2A Atezolizumab Renal cell carcinoma PD-L1 Antineoplastic Combined Chemotherapy Protocols Biomarkers Tumor Sunitinib medicine Humans Carcinoma Renal Cell Immune Checkpoint Inhibitors Randomized Controlled Trials as Topic biology Sequence Analysis RNA business.industry Gene Expression Profiling Computational Biology Prognosis medicine.disease Kidney Neoplasms Blockade Gene Expression Regulation Neoplastic Treatment Outcome 030104 developmental biology Clinical Trials Phase III as Topic Oncology 030220 oncology & carcinogenesis biology.protein Cancer research business Unsupervised Machine Learning medicine.drug |
| Zdroj: | Cancer Cell |
| ISSN: | 1535-6108 |
| Popis: | Summary Integrated multi-omics evaluation of 823 tumors from advanced renal cell carcinoma (RCC) patients identifies molecular subsets associated with differential clinical outcomes to angiogenesis blockade alone or with a checkpoint inhibitor. Unsupervised transcriptomic analysis reveals seven molecular subsets with distinct angiogenesis, immune, cell-cycle, metabolism, and stromal programs. While sunitinib and atezolizumab + bevacizumab are effective in subsets with high angiogenesis, atezolizumab + bevacizumab improves clinical benefit in tumors with high T-effector and/or cell-cycle transcription. Somatic mutations in PBRM1 and KDM5C associate with high angiogenesis and AMPK/fatty acid oxidation gene expression, while CDKN2A/B and TP53 alterations associate with increased cell-cycle and anabolic metabolism. Sarcomatoid tumors exhibit lower prevalence of PBRM1 mutations and angiogenesis markers, frequent CDKN2A/B alterations, and increased PD-L1 expression. These findings can be applied to molecularly stratify patients, explain improved outcomes of sarcomatoid tumors to checkpoint blockade versus antiangiogenics alone, and develop personalized therapies in RCC and other indications. |
| Databáze: | OpenAIRE |
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