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Breast Cancer Genome Guided Therapy Study (BEAUTY)

ABSTRACT: Breast Cancer Genome Guided Therapy Study (BEAUTY)

PROVIDER: PRJNA306903 | ENA |

REPOSITORIES: ENA

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Breast Cancer Genome Guided Therapy Study (BEAUTY)

Project description:<p>The Breast Cancer Genome Guided Therapy Study (BEAUTY) is a prospective neoadjuvant clinical study enrolling 140 women with Stage I-III breast cancer. The goals of this study were to 1) perform comprehensive sequencing of germline and tumor tissues (exome and RNA seq), 2) identify genomic alterations and perturbed pathways associated with response/resistance to standard chemotherapy, and 3) develop patient-derived xenograft (PDX) for testing of therapeutic regimens chosen on the basis of alterations identified by genetic sequencing.</p>

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Sleeping Beauty Expression data from mouse

Project description:We extracted RNA of 39 mouse tissue of various genotypes and performed expression microarrays. Subsequently a screen was conducted using the Sleeping Beauty (SB) transposon to identify breast cancer candidate genes. 39 mouse samples expression data.

2016-07-03 | E-GEOD-43263 | biostudies-arrayexpress

Sleeping Beauty Expression data from mouse

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Mechanistic Model-Guided Study of Embryonic Morphogenesis

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Single-cell profiling guided combinatorial immunotherapy for breast cancer resistance to Her2/neu and CDK4/6 targeted therapy

Project description:Single-cell profiling guided combinatorial immunotherapy for breast cancer resistance to Her2/neu and CDK4/6 targeted therapy

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Single-cell profiling guided combinatorial immunotherapy for breast cancer resistance to Her2/neu and CDK4/6 targeted therapy

Project description:Trastuzumab (Herceptin™), a humanized monoclonal antibody targeting the extracellular domain of human epidermal growth factor receptor-2 (HER2), is one of the most successful examples of targeted therapies for HER2-positive breast cancer. However, drug resistance remains daunting challenges. New combinatorial regimen of CDK4/6 inhibitors plus trastuzumab is currently under active clinical investigations. In this study, we seek to prospectively model the in vivo response to CDK4/6 inhibitor Palbociclib (Pal) plus trastuzumab (Ab) using transgenic Her2/Neu mouse model in parallel with the current clinical trial scenario. We performed single cell RNA-seqencing (Drop-seq) to profile and compare tumor cells and infiltrated immune cells derived from control, Ab+Pal sensitive/residual (APS) and resistant/progressive (APR) tumors. We revealed that although Ab+Pal treatment enhanced antigen processing, presentation and interferon signaling on tumor cells, a distinct immunosuppressive immature myeloid cells (IMCs) infiltrated in the resistant tumor microenvironment to promote resistant phenotype. Based on single cell gene set enrichment analysis (profiling) guided drug screening, we identified and evaluated a combinatorial immunotherapy regimen. We found that combinatorial immunotherapy with receptor tyrosine kinase inhibitor Cabozantinib and immune checkpoint blockades overcome Ab+Pal resistance by inhibiting IMCs and enhancing anti-tumor immunity. Moreover, our rationally designed sequential combinatorial regimens enabled durable response and sustained controlling of the emergence of acquired resistance, thus significantly improved outcomes of rapidly evolving Her2/Neu positive breast cancers. Our results implicate that single-cell RNA sequencing profiling guided combinatorial immunotherapy as a strategy to mitigate the emergence of resistance and to achieve long-term therapeutic benefit merits clinical translation.

2019-06-19 | GSE122336 | GEO

Hormone Therapy Use and Breast Tissue DNA Methylation: Analysis of Epigenome Wide Data from the Normal Breast Study

Project description:Hormone Therapy Use and Breast Tissue DNA Methylation: Analysis of Epigenome Wide Data from the Normal Breast Study

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