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Articles by Eddy Saad
Distinct endogenous retroviruses are expressed in mutational subtypes of clear cell renal cell carcinoma and are linked to improved clinical outcomes
Keywords ccRCC transposable elements endogenous retrovirus immunotherapy epigenetic Research topic(s) CP: cancer CP: molecular biology Introduction Renal cell carcinoma (RCC) is the most frequent type of primary renal neoplasm and represents approximately 2% of global cancer diagnoses.1 In the US alone, there were over 80,000 estimated cases of RCC in 2023.2,3 Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of RCC, accounting for 75% of RCC diagnoses.4 ccRCC is...
The clinical landscape of HIF2α inhibitors in oncology
Abstract Hypoxia-inducible factor 2α (HIF2α; also known as endothelial PAS domain-containing protein 1) had long been considered an undruggable transcription factor until the discovery of an allosteric pocket within its PAS-B domain enabled the development of selective small-molecule antagonists.
Single-cell epigenetic profiling reveals a tumor-intrinsic interferon response program in ccRCC tied to poor prognosis and BAP1 loss
Abstract Transcriptional programs in renal cell carcinoma (RCC) have been linked to tumor heterogeneity and clinical outcomes, but analogous efforts to define chromatin programs shaping disease biology have been limited. Here, we generated single-cell ATAC-seq profiles from patients with RCC and integrated them with three previously published datasets to identify chromatin programs in tumor cells.
A context-augmented large language model for accurate precision oncology medicine recommendations
Results Given the critical role of prompt optimization in enhancing LLM performance, we first evaluated whether designing a specific prompt structure would optimize the accuracy of a representative LLM (Mistral Nemo 12B) in accurately retrieving FDA-approved biomarker-based (“precision”) oncology therapies.25 We tested four distinct prompt strategies (see STAR MethodsTable 1). All evaluated queries were formulated using the structured data from MOAlmanac v2024-04-11 (Tables S1 and S2).
Myeloid cells mediate interferon-driven resistance to immunotherapy in advanced renal cell carcinoma
Keywords renal cell carcinoma immunotherapy immunotherapy resistance cancer immunology tumor immunology interferon signaling IFNs myeloid cells tumor-associated macrophages Introduction Immune checkpoint blockade (ICB) has become a crucial component of first-line management of advanced renal cell carcinoma (RCC).1,2,3,4,5,6 However, RCC immunobiology is distinct from that of other immunotherapy-responsive cancer types.
Single-cell epigenetic profiling reveals an interferon response-high program associated with BAP1 deficiency in kidney cancer
Abstract Renal cell carcinoma (RCC) is characterized by recurrent somatic mutations in epigenetic regulators, which stratify patients into clinically significant subgroups with distinct prognoses and treatment responses. However, the cell type-specific epigenetic landscape of RCC—broadly and in the context of these mutations—is incompletely understood. To investigate these open questions, we integrated single nucleus ATAC sequencing data from RCC tumors across four independent cohorts.
Volume 29 Issue Supplement_1
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Understanding Mechanisms Behind Acquired Resistance to Immunotherapy in Metastatic Renal Cell Carcinoma
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