Choueiri Lab Research
Research Areas
Using Multi-omic Approaches Such As Genomics, Transcriptomics, and Metabolomics
We defined the respective contributions of somatic and germline alterations in renal cell carcinoma to recurrence in early-stage disease and therapeutic response to systemic therapy, including immune checkpoint blockers, in metastatic disease.
Selected publications:
- Schutz FA, et al…Choueiri TK (2013). Single nucleotide polymorphisms and risk of recurrence of renal-cell carcinoma: a cohort study. Lancet Oncol;14:81-7. PMCID: PMC3769687.
View in PubMed - Miao D, et al…Choueiri TK*, Van Allen EM* (2018). Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science;359:801-6. PMCID: PMC6035749 (*equal contribution).
View in PubMed - Braun DA, et al…Choueiri TK (2020). Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma. Nat Med;26:909-18. PMCID: PMC7499153.
View in PubMed - Choueiri TK, et al. (2024). Integrative Analyses of Tumor and Peripheral Biomarkers in the Treatment of Advanced Renal Cell Carcinoma. Cancer Discov;14(3):406-23. PMID: 38385846; PMCID: PMC10905671.
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Novel Technologies in Renal Cell Carcinoma
Including the use of single cell sequencing of renall cell carcinoma tumors across stages to dissect the immune microenvironment of kidney cancer. We were the first to characterize plasma and urine cell-free (cf) methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) as a highly sensitive assay capable of detecting GU cancers at an early stage to reduce cancer-related mortality, and compared it to the commonly used plasma cfDNA variant analysis
Selected publications:
- Nuzzo PV, et al…De Carvalho DD*, Choueiri TK*, Freedman ML* (2020). Detection of renal cell carcinoma using plasma and urine cell-free DNA methylomes. Nat Med;26:1041-3. PMCID: PMC8288043 (*equal contribution).
View in PubMed - Braun DA, et al…Choueiri TK*, Wu CJ* (2021). Progressive immune dysfunction with advancing disease stage in renal cell carcinoma. Cancer Cell;39(5):632-48. PMCID: PMC8138872 (*equal contribution).
View in PubMed - Lasseter K, et al…Choueiri TK*, Kwiatkowski DJ* (2020). Plasma cell-free DNA variant analysis compared with methylated DNA analysis in renal cell carcinoma. Genet Med;22:1366-73. PMID: 32341571 (*equal contribution).
View in PubMed - Bi K, et al…Choueiri TK*, Van Allen EM* (2021). Tumor and immune reprogramming during immunotherapy in advanced renal cell carcinoma. Cancer Cell;39(5):649-61. PMCID: PMC8115394 (*equal contribution).View in PubMed
Understanding the Biology of Rare Variants of RCC
Our work has contributed to the molecular characterization of rare kidney cancer variants, including discovering BRAF gene mutations in metanephric adenoma of the kidney; shedding light on the biology of response to MET inhibitors in a subset of papillary RCCs; and defining the molecular and immune landscape of sarcomatoid RCC, a highly aggressive form of kidney cancer, as well as translocation RCC. Dr. Choueiri also played an integral part in the chromophobe and papillary RCC TCGA working groups.
Selected publications:
- Choueiri TK, et al. (2012). BRAF Mutations in Metanephric Adenoma of the Kidney. Eur Urol;62(5):917-22. PMCID: PMC4516083.
View in PubMed - Choueiri TK, et al. (2020). Efficacy of Savolitinib vs Sunitinib in Patients With MET-Driven Papillary Renal Cell Carcinoma: The SAVOIR Phase 3 Randomized Clinical Trial. JAMA Oncol;6(8):1247-55. PMCID: PMC7260692.
View in PubMed - Bakouny Z, et al…Choueiri TK (2021). Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma. Nat Commun;12:808. PMCID: PMC7865061.
View in PubMed - Bakouny Z, et al…Choueiri TK*, Viswanathan SR* (2022). Integrative clinical and molecular characterization of translocation renal cell carcinoma. Cell Rep;38(1):110190. PMCID: PMC9127595 (*equal contribution)
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Choueiri, T.K., Kaelin, W.G. Targeting the HIF2–VEGF axis in renal cell carcinoma. Nat Med 26, 1519–1530 (2020). https://doi.org/10.1038/s41591-020-1093-z -
Bakouny, Z., Braun, D.A., Shukla, S.A. et al. Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma. Nat Commun 12, 808 (2021). https://doi.org/10.1038/s41467-021-21068-9
Translating Pre-clinical Research Into Pivotal Randomized Trials
Dr. Choueiri has effectively translated pre-clinical research by leading several pivotal randomized trials from early- to late-stage development, resulting in the FDA approval of several drugs and combinations that have defined the RCC therapeutic landscape, in both the metastatic and adjuvant settings.
Selected publications:
- Choueiri TK, et al…KEYNOTE-564 Investigators (2024). Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma. N Engl J Med;390(15):1359-1371. doi:10.1056/NEJMoa2312695
View in PubMed - Choueiri TK, et al…CheckMate 9ER Investigators (2021). Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med;384(9):829-41. PMCID: PMC8436591.
View in PubMed - Motzer R, et al…Choueiri TK; CLEAR Trial Investigators (2021). Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med;384(14):1289-300. PMID: 33616314.
View in PubMed - Choueiri TK, et al…COSMIC-313 Investigators (2023). Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. N Engl J Med;388(19)1767-1778. PMCID: PMC10257898
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International Metastatic RCC Database Consortium (IMDC)
Co-founding the International Metastatic RCC Database Consortium (IMDC), which comprises tumor biospecimens, clinical characteristics, and outcomes for patients all over the world with advanced/metastatic RCC on systemic therapy. Since its inception it has become the largest contemporary database of advanced RCC patients. Prognostic criteria derived from patient risk factors are now widely used for prognostication and clinical trials stratification of novel agents. We are now leveraging IMDC biospecimen cohorts to search for understand the underlying biology of advanced RCC and the determinants of therapeutic response and resistance.
Click here to open the IMDC website.
Selected publications:
- Heng DYC, et al…Choueiri TK (2009). Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol;27(34):5794-9. PMID: 19826129.
View in PubMed - Heng DYC, et al…Choueiri TK (2013). External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study. Lancet Oncol;14(2):141-8. PMCID: PMC4144042.
View in PubMed - Albiges L, et al…Choueiri TK (2016). Body Mass Index and Metastatic Renal Cell Carcinoma: Clinical and Biological Correlations. J Clin Oncol;34(30):3655-63. PMCID: PMC5065111.
View in PubMed - Lalani AK, et al…Choueiri TK (2021). Assessment of Immune Checkpoint Inhibitors and Genomic Alterations by Body Mass Index in Advanced Renal Cell Carcinoma. JAMA Oncol;7(5):773-5. PMCID: PMC7934079
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