7081 results for "canc*"

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• The dataset for Genome-wide analyses of cell-free DNA for therapeutic monitoring of patients with pancreatic cancer

  The dataset for “Genome-wide analyses of cell-free DNA for therapeutic monitoring of patients with pancreatic cancer” includes 496 cram files from whole genome next-generation sequencing on the Illumina NovaSeq 6000. The samples analyzed include tumor tissue, matched buffy coat and longitudinal plasma samples from individuals with pancreatic cancer.

  Dataset EGAD50000001353

• The data access committee for Genome-wide analyses of cell-free DNA for therapeutic monitoring of patients with pancreatic cancer

  Dac EGAC50000000588

• APOBEC Breast Cancer Whole Genome

  Five tumor-normal human breast cancer cases driven by APOBEC mutagenesis, including normal tissue, primary, and metastatic samples for each patient.

  Dataset EGAD50000001275

• Total RNAseq data from 8 patients with muscle invasive bladder cancer

  For this dataset we performed total RNAseq on blood samples from 8 patients with muscle invasive bladder cancer. The data consists of 8 sets of paired fastq files with accompanying UMI fastq files. Sequenced on the Illumina NoveSeq6000 platform using S2 flow cells (v1.5,2x150 cycles), with a mean yield of 313 million reads.

  Dataset EGAD50000001380

• Single cell RNAseq and TCRseq data from tumor and blood samples from 4 patients with muscle invasive bladder cancer

  For this dataset we performed single cell RNAseq paired with single cell TCR-seq on tumor and blood samples from 4 patients. This dataset contains 4 tumor samples as well as 4 blood samples. Each sample is made up of 2 sets of paired fastq files. The first pair contains reads corresponding to RNA transcripts (_Transcripts in file name), while the second pair contain reads corresponding to TCRs (_VDJ in file name). Sequenced on the Illumina NovaSeq6000 platform in a paired-end run using an SP flow cell (v1.5, 300 cycles).

  Dataset EGAD50000001381

• Bulk TCRseq data from 149 patients with bladder cancer

  For this dataset we performed bulk TCRseq on tumor and serial blood samples from patients with muscle invasive bladder cancer (n patients = 119, n blood = 209, n tumor = 28) or non-muscle invasive bladder cancer (n patients = 30, n blood = 56, n tumor = 19) for a total of 149 patients and 312 samples. Each sample consists of a paired fastq file. Sequenced on the Ilumina NovaSeq6000 platform using SP and S1 flow cells (v1.5, 2x101 cycles), with a mean yield of 42 million reads covering the CDR3β region.

  Dataset EGAD50000001382

• Subclonal variation in patients with pediatric T-lymphoblastic leukemia (T-ALL)

  Variations in TP53 and KRAS genes indicate a particularly poor prognosis in relapsed pediatric T-ALL. We hypothesized that these variations might be subclonally present at disease onset and contribute to relapse risk. To test this, we examined 386 children diagnosed with T-ALL, including more than 100 patients who relapsed as well as matched non-relapsing controls.

  Study EGAS50000000794

• PanCancer_Phosphoproteomics2024

  Pan-cancer phosphoproteomics profiling data for 1000 retrospective and prospective samples of the MASTER/INFORM cohort,Shotgun proteomics

  Dataset EGAD00010002730

• A Randomized Trial of Combined PD-L1 and CTLA-4 Inhibition with Targeted Low-Dose or Hypofractionated Radiation for Patients with Metastatic Colorectal Cancer

  Brief SummaryThis randomized phase II trial studies the side effects of durvalumab and tremelimumab to see how well they work with or without high or low-dose radiation therapy in treating patients with colorectal (CRC) or non-small cell lung cancer (NSCLC) that has spread to other parts of the body (metastatic). Immunotherapy with durvalumab and tremelimumab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving durvalumab and tremelimumab with radiation therapy may work better in treating patients with colorectal or non-small cell lung cancer.Detailed DescriptionPRIMARY OBJECTIVES:I. To assess safety and tolerability of combined checkpoint blockade with MEDI4736 (durvalumab) and tremelimumab alone or with high or low-dose radiation in non-small cell lung cancer (NSCLC). (NSCLC Cohort) II. To compare the overall response (excluding the irradiated lesion[s]) between combined checkpoint blockade with MEDI4736 and tremelimumab alone or combined checkpoint blockade with low or high dose radiation. (NSCLC Cohort) III. To assess safety and tolerability of combined checkpoint blockade with MEDI4736 and tremelimumab with high or low-dose radiation. (Colorectal Cohort) IV. To determine the overall response rate (excluding the irradiated lesion[s]) with combined checkpoint blockade with MEDI4736 and tremelimumab with either low or high dose radiation. (Colorectal Cohort)SECONDARY OBJECTIVES:I. To estimate median progression-free survival and overall survival. (NSCLC Cohort) II. To determine local control within the irradiated field(s) and abscopal response rates. (NSCLC Cohort) III. To evaluate associations between PD-L1 expression as well as levels of infiltrating CD3+, CD8+ T-cells and overall response. (NSCLC Cohort) IV. To explore changes in PD-L1 expression, circulating T-cell populations, T-cell infiltration, ribonucleic acid (RNA) expression, spatial relationship of immune markers, and mutational burden as a result of low or high dose radiation. (NSCLC Cohort) V. To estimate median progression-free survival and overall survival. (Colorectal Cohort) VI. To determine local control within the irradiated field and abscopal response rates. (Colorectal Cohort) VII. To evaluate associations between PD-L1 expression as well as levels of infiltrating CD3+ CD8+ T-cells and overall response. (Colorectal Cohort) VIII. To evaluate changes between PD-L1 expression as well as levels of infiltrating CD3+, CD8+ T-cells induced by targeted low or high dose radiation. (Colorectal Cohort) IX. To explore changes in circulating T-cell populations, T-cell infiltration, RNA expression, spatial relationship of immune markers, and mutational burden as a result of low or high dose radiation. (Colorectal Cohort)OUTLINE: Patients are assigned to 1 of 2 cohorts. NOTE: This Study is only for Cohort 2. Please see phs003295 for Cohort 1COHORT 1: Patients with NSCLC are randomized to 1 of 3 arms.ARM A: Patients receive tremelimumab and durvalumab and as in Arm C. Beginning at week 2, patients receive high dose radiation therapy once per day (QD) over 10 days for up to 3 fractions.ARM B: Patients receive tremelimumab and durvalumab and as in Arm C. Beginning at week 2, patients receive low dose radiation therapy every 6 hours twice per day (BID) on weeks 2, 6, 10 and 14.ARM C: Patients receive tremelimumab intravenously (IV) and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses.COHORT 2: Patients with CRC are randomized to 1 of 2 arms.ARM A: Patients receive tremelimumab intravenously (IV) and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses. Beginning at week 2, patients receive high dose radiation therapy once per day (QD) over 10 days for up to 3 fractions.ARM B: Patients receive tremelimumab intravenously (IV) and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses. Beginning at week 2, patients receive low dose radiation therapy every 6 hours twice per day (BID) on weeks 2, 6, 10 and 14.After completion of study treatment, patients are followed for up to 12 weeks.Official TitleA Phase 2 Study of MEDI4736 (Durvalumab) and Tremelimumab Alone or in Combination With High or Low-Dose Radiation in Metastatic Colorectal and NSCLC Conditions Metastatic Colorectal CarcinomaMetastatic Lung Non-Small Cell CarcinomaStage IV Colorectal Cancer AJCC v7Stage IV Lung Non-Small Cell Cancer AJCC v7Stage IVA Colorectal Cancer AJCC v7Stage IVB Colorectal Cancer AJCC v7 Intervention/Treatment Biological: DurvalumabRadiation: Radiation TherapyBiological: Tremelimumab Other Study ID Numbers NCI-2016-01325NCI-2016-01325 ( Registry Identifier ) (REGISTRY: CTRP (Clinical Trial Reporting Program))17-71910021 ( Other Identifier ) (OTHER: Dana-Farber - Harvard Cancer Center LAO)10021 ( Other Identifier ) (OTHER: CTEP) Molecular Technologies/AssaysIHCmIFOlinkCyTOFRNAseqWES

  Study phs003294

• Durvalumab Plus Tremelimumab Alone or in Combination with Low-Dose or Hypofractionated Radiotherapy in Metastatic Non-Small-Cell Lung Cancer Refractory to Previous PD(L)-1 Therapy: an Open-Label, Multicentre, Randomised, Phase 2 Trial

  Brief SummaryThis randomized phase II trial studies the side effects of durvalumab and tremelimumab and to see how well they work with or without high or low-dose radiation therapy in treating patients with colorectal or non-small cell lung cancer that has spread to other parts of the body (metastatic). Immunotherapy with durvalumab and tremelimumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving durvalumab and tremelimumab with radiation therapy may work better in treating patients with colorectal or non-small cell lung cancer.Detailed DescriptionPRIMARY OBJECTIVES:I. To assess safety and tolerability of combined checkpoint blockade with MEDI4736 (durvalumab) and tremelimumab alone or with high or low-dose radiation in non-small cell lung cancer (NSCLC). (NSCLC Cohort) II. To compare the overall response (excluding the irradiated lesion[s]) between combined checkpoint blockade with MEDI4736 and tremelimumab alone or combined checkpoint blockade with low or high dose radiation. (NSCLC Cohort) III. To assess safety and tolerability of combined checkpoint blockade with MEDI4736 and tremelimumab with high or low-dose radiation. (Colorectal Cohort) IV. To determine the overall response rate (excluding the irradiated lesion[s]) with combined checkpoint blockade with MEDI4736 and tremelimumab with either low or high dose radiation. (Colorectal Cohort)SECONDARY OBJECTIVES:I. To estimate median progression-free survival and overall survival. (NSCLC Cohort) II. To determine local control within the irradiated field(s) and abscopal response rates. (NSCLC Cohort) III. To evaluate associations between PD-L1 expression as well as levels of infiltrating CD3+, CD8+ T-cells and overall response. (NSCLC Cohort) IV. To explore changes in PD-L1 expression, circulating T-cell populations, T-cell infiltration, ribonucleic acid (RNA) expression, spatial relationship of immune markers, and mutational burden as a result of low or high dose radiation. (NSCLC Cohort) V. To estimate median progression-free survival and overall survival. (Colorectal Cohort) VI. To determine local control within the irradiated field and abscopal response rates. (Colorectal Cohort) VII. To evaluate associations between PD-L1 expression as well as levels of infiltrating CD3+ CD8+ T-cells and overall response. (Colorectal Cohort) VIII. To evaluate changes between PD-L1 expression as well as levels of infiltrating CD3+, CD8+ T-cells induced by targeted low or high dose radiation. (Colorectal Cohort) IX. To explore changes in circulating T-cell populations, T-cell infiltration, RNA expression, spatial relationship of immune markers, and mutational burden as a result of low or high dose radiation. (Colorectal Cohort)OUTLINE: Patients are assigned to 1 of 2 cohorts. NOTE: This Study is only for Cohort 1. Please see phs003294 for Cohort 2COHORT 1: Patients with NSCLC are randomized to 1 of 3 arms.ARM A: Patients receive tremelimumab and durvalumab and as in Arm C. Beginning at week 2, patients receive high dose radiation therapy once per day (QD) over 10 days for up to 3 fractions.ARM B: Patients receive tremelimumab and durvalumab and as in Arm C. Beginning at week 2, patients receive low dose radiation therapy every 6 hours twice per day (BID) on weeks 2, 6, 10 and 14.ARM C: Patients receive tremelimumab intravenously (IV) and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses.COHORT 2: Patients with CRC are randomized to 1 of 2 arms.ARM A: Patients receive tremelimumab intravenously (IV) and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses. Beginning at week 2, patients receive high dose radiation therapy once per day (QD) over 10 days for up to 3 fractions.ARM B: Patients receive tremelimumab intravenously (IV) and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses. Beginning at week 2, patients receive low dose radiation therapy every 6 hours twice per day (BID) on weeks 2, 6, 10 and 14.After completion of study treatment, patients are followed for up to 12 weeks.Official TitleA Phase 2 Study of MEDI4736 (Durvalumab) and Tremelimumab Alone or in Combination With High or Low-Dose Radiation in Metastatic Colorectal and NSCLC Conditions Metastatic Colorectal CarcinomaMetastatic Lung Non-Small Cell CarcinomaStage IV Colorectal Cancer AJCC v7Stage IV Lung Non-Small Cell Cancer AJCC v7Stage IVA Colorectal Cancer AJCC v7Stage IVB Colorectal Cancer AJCC v7 Intervention/Treatment Biological: DurvalumabRadiation: Radiation TherapyBiological: Tremelimumab Other Study ID Numbers NCI-2016-01325NCI-2016-01325 ( Registry Identifier ) (REGISTRY: CTRP (Clinical Trial Reporting Program))17-71910021 ( Other Identifier ) (OTHER: Dana-Farber - Harvard Cancer Center LAO)10021 ( Other Identifier ) (OTHER: CTEP) Molecular Technologies / AssaysCyTOFIHCmIFOlinkRNAseqWES

  Study phs003295

• Sequencing of 3D Organoids Derived From Colorectal Cancer Patients

  This study focuses on the whole-exome sequencing (WES) of patient-derived organoids (PDOs) established from colorectal cancer (CRC) tumors collected at Columbia University. CRC remains a major cause of cancer-related mortality due to its metastatic progression and resistance to therapy. To model CRC at the patient level, we generated 3D organoid cultures from primary and metastatic tumors, preserving their genetic and phenotypic characteristics. The study cohort consists of 9 CRC patients with microsatellite-stable adenocarcinomas from the ascending, transverse, and descending colon, as well as the rectum, with differentiation statuses ranging from well to moderate and moderate-poor. Notably, for one patient, we generated organoids from both the primary tumor and matched liver metastases, allowing for a comparative analysis of tumor evolution. PDOs were derived from these tumors and subjected to WES at early passage to profile somatic mutations, copy number variations, and other genomic alterations to identify mutational signatures. Mutations identified in the PDOs were cross-referenced and confirmed with mutational data from the Columbia Solid Tumor Panel, which was conducted on all tumor tissues prior to organoid establishment. Molecular technologies employed include next-generation sequencing (NGS) for WES, enabling high-resolution characterization of the genomic landscape of CRC PDOs. WES of PDOs allowed us to classify tumor samples based on oncogenic mutations and mutation types, with a specific focus on PIK3CA. Notably, the efficacy of PI3Kα-specific pharmacologic inhibitors in suppressing organoid growth was dependent on the mutational status of KRAS and PIK3CA, underscoring the importance of genomic context in therapeutic response. The dataset available through dbGaP includes raw WES data from CRC PDOs.

  Study phs003965

• Childhood Cancer Data Initiative (CCDI): Comprehensive Genomic Sequencing of Pediatric Cancer Cases (CMRI/KUCC)

  This study provides paired tumor normal genomic sequencing data from ~ 200 children with cancer, including both solid tumors and leukemias, done by the Children's Mercy Research Institute (CMRI) and University of Kansas Cancer Center (KUCC). These data include whole genome sequencing (generally, ~20x), whole exome sequencing (generally, ~300x), bulk RNA sequencing (generally, ~80 million reads), and single-cell RNA and ATAC sequencing (>50,000 reads/cell). Additional phenotypic, pathologic, and genetic data, gathered clinically for these samples, are also provided.

  Study phs002529

• DirectHRD Enables Sensitive Scar-Based Classification of Homologous Recombination Deficiency (HRD)

  Homologous recombination deficiency (HRD)-induced genomic scars are an FDA-approved biomarker for identifying cancers likely to respond to PARP inhibitors. However, detecting HRD scars from blood biopsies has been challenging due to the low tumor content in blood samples. To address this limitation, we developed DirectHRD, a genomic scar-based HRD classifier leveraging whole-genome sequencing (WGS) data for non-invasive blood biopsy testing. DirectHRD was applied to 90 cell-free DNA (cfDNA) samples across four cancer types: breast, ovarian, prostate, and pancreatic. The method achieved an AUC of 0.87 and demonstrated the ability to detect HRD at tumor fractions as low as 1%, offering a tenfold increase in sensitivity compared to state-of-the-art methods.

  Study phs003760

• Genomic Changes in Breast Cancer Among Chinese Women in Hong Kong

  Recently, tumor sequencing and profiling analyses have improved molecular classification and refined existing breast cancer subtypes. However, epidemiologic data are absent in most somatic profiling studies even in extensively studied Western populations. The expansion of genomic studies to understudied populations with the integration of etiologic factors will allow the capture of a much wider range of genetic structure and mutagenic exposures associated with breast cancer risk. We therefore conducted a detailed molecular characterization of paired breast tumor/normal tissues using fresh frozen tissues collected from breast cancer cases in an ongoing breast cancer case-control study in Hong Kong. These analyses included whole genome (WGS)/exome sequencing (WES), targeted DNA panel sequencing, RNA sequencing (RNA-Seq), and genome-wide methylation profiling analyses.

  Study phs001870

• A Comprehensive Genetic Study of Classical Hodgkin Lymphoma Using Circulating Tumour DNA

  This study on classical Hodgkin lymphoma (cHL) used advanced methods to analyse circulating tumour DNA (ctDNA) in 297 cases, offering insights into its genetic landscape and linking it to disease pathophysiology and clinical progression. Key findings include the identification of whole genome duplication as a predictor of poor chemotherapy response. Additionally, a highly recurrent somatic expression quantitative trait locus of the BCL6 gene was discovered, implicating regulatory mutations in cHL pathophysiology and highlighting BCL6 as both a vulnerability and therapeutic target. Consensus clustering identified two cHL subtypes distinguished by the underlying mechanisms of genetic instability, rather than by specific genetic mutations or EBV infection. The study also linked the number and clonality of neoantigens with tumour microenvironment and response to checkpoint blockade. Finally, our results suggested ctDNA analysis as a tool to distinguish ambiguous PET/CT-positive lesions persisting after treatment, aiming to reduce unnecessary medical interventions.

  Study EGAS50000000873

• Shallow whole genome sequencing DETECT samples

  Shallow whole genome sequencing of samples from the paper Beddowes et al. A large-scale retrospective study in metastatic breast cancer patients using circulating tumour DNA and machine learning to predict treatment outcome and progression-free survival. Mol. One 2025. This includes 1048 longitudinal plasma samples from 149 patients and 35 normals. Samples were sequenced with shallow whole genome sequencing for copy number estimation. All the files are single-end fastq files.

  Dataset EGAD50000001333

• Biopsy-Derived Organoids in Personalised Early Breast Cancer Care: Challenges of Tumour Purity and Normal Cell Overgrowth Cap Their Practical Utility

  The ability to establish organoids composed exclusively of tumour rather than healthy cells is essential for their implementation into clinical practice. Organoids have in recent years emerged as a powerful tool to expand patient material in culture and generate modifiable 3D models derived from humans or animal models. For translational research, they enable the creation of model systems for an ever-increasing number of cell types and diseases. And in personalised medicine, they potentially allow for functional drug testing with high predictive power in certain settings. We found that using biopsy material from untreated, early-stage primary breast cancer patients poses significant challenges for consistently culturing tumour cells as organoids. Specifically, we observed frequent outgrowth of genetically normal, non-cancerous epithelial cells. We analysed >100 biopsy samples from early-stage breast cancer and present our large collection of >70 organoid lines. We also show methods of assessing successful tumour cell culture in a time and cost-efficient manner, proving a high rate (>85%) of normal cell overgrowth in early-stage breast cancer organoids. Finally, we show a number of successful attempts to culture cancer organoids from mastectomy-derived tissue of advanced, metastatic breast cancer. We conclude that the usefulness of organoids from early breast cancer for translational research and personalised medicine, especially guidance of adjuvant or post-surgical maintenance therapy, is strongly limited by the low success rate of culturing cancerous cells under organoid conditions.

  Study EGAS50000000605

• Stratified Medicine Paediatrics (SMPaeds): molecular profiling of relapsed paediatric cancer

  We profiled a large heterogenous cohort of matched diagnostic-relapse tumour tissue and plasma-derived cell free DNA (cfDNA) from patients with relapsed and progressive solid tumours of childhood. Tumour DNA and cfDNA were analysed by targeted panel sequencing and low coverage whole genome sequencing.

  Study EGAS50000000549

• The genomic basis of childhood T-lineage acute lymphoblastic leukemia

  T-lineage acute lymphoblastic leukemia (T-ALL) is a high-risk tumor that has eluded comprehensive genomic characterization, in part due to the high frequency of non-coding genomic alterations resulting in oncogenic dysregulation. Here we report integrated genome and transcriptome sequencing of T-ALL tumor and remission samples obtained from over 1300 uniformly treated children with T-ALL, coupled with epigenomic and single cell analysis of malignant and normal T cell precursors. Integrated analysis identified 15 subtypes with distinct genomic drivers, gene expression, developmental state and outcome. Integration with chromatin topology analyses enabled elucidation of multiple mechanisms of enhancer deregulation that involve enhancers and genes in a subtype-specific fashion. We show that the immunophenotypically-described, high-risk entity of early T-cell precursor ALL is superseded by a broader category of leukemias of variable immunophenotype with diverse genomic alterations of a core set of genes encoding regulators of hematopoietic stem cell development. Numerous genetic alterations and disease subtypes emerged as independent predictors of survival and treatment failure in univariable and multivariable outcome models. These findings provide a roadmap for the classification, risk stratification and mechanistic understanding of this disease.

  Study EGAS50000000016

• Identification and targeting of extremely high-risk gamma delta T-ALL in children

  Acute lymphoblastic leukemia expressing the gamma delta T cell receptor (γδ T-ALL) is an uncommon, poorly understood disease. We studied 200 pediatric γδ T-ALL enrolled on clinical trials to understand the clinical and genetic features of this disease, which showed variation in outcome according to age and genetic driver. γδ T-ALL diagnosed in children under three years of age was extremely high-risk and enriched for genetic alterations leading to both LMO2 activation and STAG2 inactivation. Using patient samples and isogenic cell lines, we show that inactivation of STAG2 profoundly perturbs chromatin organization by altering enhancer-promoter looping and results in deregulation of gene expression related to T-cell differentiation. High throughput drug screening identified a vulnerability in DNA repair pathways arising from STAG2 inactivation, which was efficaciously targeted by PARP inhibition. These data provide a diagnostic and therapeutic framework for classification and risk stratification of pediatric γδ T-ALL.

  Study EGAS50000000018

• Spatially Resolved Tumor Ecosystems and Cell States in Gastric Adenocarcinoma Progression and Evolution

  Gastric cancer (GC) is a major cause of global cancer mortality with high levels of heterogeneity, and intratumoral heterogeneity (ITH) represents a significant barrier to GC patient outcomes. In this study, we applied GeoMx DSP technology to identify ITH in GC. We found spatially colocalized RNA-based intratumor subgroups within samples, each correlated with distinct spatially oriented TME and immune profiles. The findings broadening our understanding of the spatial and molecular complexity of GC ITH and offering a valuable data resource for future exploration and discovery.

  Study EGAS50000000345

• Singapore Gastric Cancer Consortium GeoMx DSP tissue microarray (SGCC TMA) cohort

  Gastric cancer (GC) remains a significant global health challenge due to its high heterogeneity, with intratumoral heterogeneity (ITH) posing a major obstacle to effective patient outcomes. In this study, utilizing GeoMx Digital Spatial Profiler (DSP) technology, we specifically investigated ITH within GC patients by comparing tumor core regions to tumor edge regions. Our findings indicate that tumor edge regions exhibit more advanced tumor activity, akin to the G2-like progressed state, compared to tumor core regions. The findings confirm the spatial locations of G2 RNA-ITH subregions and support the conclusions drawn from the discovery cohort.

  Study EGAS50000000640

• Bladder cancer subtyping study across 4 atezo clinical trials

  Checkpoint inhibitors targeting the PD-1/PD-L1 interaction have revolutionized cancer therapy across many indications. In urothelial carcinoma (UC), several PD-1/PD-L1 inhibitors have been approved for treatment in localized and metastatic disease. While these agents provide durable clinical benefit in a number of patients, the majority do not respond. A better understanding of the molecular mechanisms underlying response and resistance is needed to tailor existing treatments and develop new therapeutics in UC. We profiled tumors from 2803 patients from four late-stage randomized clinical trials evaluating the PD-L1 inhibitor atezolizumab in metastatic UC and muscle-invasive bladder cancer by RNA-seq, a targeted DNA panel, immunohistochemistry, and digital pathology. A machine learning algorithm identified four UC transcriptional subtypes, representing luminal desert, stromal, immune, and basal tumors. Overall survival benefit from atezolizumab over standard-of-care was observed in immune and basal tumors (45% of patients). Digital pathology showed enrichment of human interpretable features in specific molecular subtypes, and a self-supervised approach could classify molecular subtypes from H&E slides with high accuracy, suggesting that machine-based image interpretation could accelerate tumor molecular profiling. Somatic alterations showed limited capacity to identify responders. Finally, mechanisms of benefit with PD-L1 blockade appeared different in immune and basal tumors, with immune tumors benefiting from B/plasma cell enrichment, while basal tumors benefited from granulocyte enrichment. This study represents the largest integration of UC molecular and curated clinical data in randomized clinical trials to date, paving the way for prospective clinical studies tailoring treatment regimens to specific tumor molecular subtypes in UC and other indications.

  Study EGAS50000000497

• The WID-EC test for the detection and risk prediction of endometrial cancer

  Study EGAS00001005033

• The DNA methylome of cervical cells and risk of ovarian cancer

  Study EGAS00001005045