Publications by authors named "Aaron D Valentine"

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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Trace amine-associated receptor 1 (rodent Taar1/human TAAR1) is a G protein-coupled receptor that is mainly recognized for its functions in neuromodulation. Previous in vitro studies suggested that Taar1 may signal from intracellular compartments. However, we have shown Taar1 to localize apically and on ciliary extensions in rodent thyrocytes, suggesting that at least in the thyroid, Taar1 may signal from the cilia at the apical plasma membrane domain of thyrocytes in situ, where it is exposed to the content of the follicle lumen containing putative Taar1 ligands.

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