Publications by authors named "David C Boyd"

Article Synopsis
  • Breast cancer's complexity necessitates a deeper understanding of cellular diversity to improve treatment methods, particularly by studying genetic variations in its subtypes at a single-cell level.
  • This study integrates single-cell RNA sequencing from various sources, resulting in a diverse dataset of 117 samples, which include different breast cancer subtypes like HR+, HER2+, and TNBC, to analyze similarities and differences across models.
  • Results show that PDX models better reflect patient samples than TNBC cell lines, with therapeutic efficacy linked to subtype proportions, underscoring the importance of these findings for preclinical research decisions in breast cancer treatment development.*
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Article Synopsis
  • Breast cancer is the leading cause of cancer deaths in women, with estrogen receptor positive (ER+) being the most common subtype.
  • Improved survival rates for ER+ breast cancer patients are largely thanks to antiestrogen treatments like tamoxifen, but about 30% of patients face recurrence and treatment resistance.
  • This study identifies two new combination therapies (simeprevir and VX-680) that, when paired with tamoxifen, significantly lower tumor levels in animal models and could enhance the effectiveness of tamoxifen in treating ER+ breast cancer.
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Article Synopsis
  • Basal-like triple-negative breast cancer (TNBC) is tough to treat because of its resistance mechanisms, but it typically has a highly active PI3K pathway instead of PIK3CA mutations.
  • BYL-719, a PIK3CA inhibitor with minimal drug interactions, has shown promise in combination therapies, particularly in cases where other treatments have failed.
  • Research using patient-derived xenografts identified effective drug combinations involving BYL-719 and other compounds, suggesting a new treatment approach for cancers driven by PIK3CA and related pathways.
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The goals of this study were to identify transcriptomic changes that arise in basal-like breast cancer cells during the development of resistance to epidermal growth factor receptor inhibitors (EGFRi) and to identify drugs that are cytotoxic once EGFRi resistance occurs. Human patient-derived xenografts (PDXs) were grown in immunodeficient mice and treated with a set of EGFRi; the EGFRi erlotinib was selected for more expansive in vivo studies. Single-cell RNA sequencing was performed on mammary tumors from the basal-like PDX WHIM2 that was treated with vehicle or erlotinib for 9 weeks.

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Background: Sequencing of patient-derived xenograft (PDX) mouse models allows investigation of the molecular mechanisms of human tumor samples engrafted in a mouse host. Thus, both human and mouse genetic material is sequenced. Several methods have been developed to remove mouse sequencing reads from RNA-seq or exome sequencing PDX data and improve the downstream signal.

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The expression of cellular reporters to label cancer cells, such as green fluorescent protein (GFP) and luciferase, can stimulate immune responses and effect tumor growth. Recently, a mouse model that expresses GFP and luciferase in the anterior pituitary gland was generated to tolerize mice to these proteins; the "Glowing Head" mouse. Mice were obtained from a commercial vendor, bred, and then used for tumor growth and metastasis studies.

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