Publications by authors named "Anne McLaren-Douglas"

The protocol Drug Sensitivity Assays of Human Cancer Organoid Cultures has now been made available open access under a CC BY 4.0 license.

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Article Synopsis
  • Breast cancer research requires models that accurately reflect the variety within tumors, and we've developed a significant collection of patient-derived tumor xenografts (PDTXs) that maintain the original tumors' characteristics in mice.
  • Our method integrates in vivo growth of PDTXs with short-term cultures of tumor cells derived from these xenografts, successfully preserving the complex genomic structure found in the original tumors.
  • We have created a biobank that serves as a valuable resource for pharmacogenomic studies, enabling the exploration of drug responses and the identification of biomarkers for treatment efficacy or resistance.
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Drug sensitivity testing utilizing preclinical disease models such as cancer cell lines is an important and widely used tool for drug development. Importantly, when combined with molecular data such as gene copy number variation or somatic coding mutations, associations between drug sensitivity and molecular data can be used to develop markers to guide patient therapies. The use of organoids as a preclinical cancer model has become possible following recent work demonstrating that organoid cultures can be derived from patient tumors with a high rate of success.

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In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. We report the establishment of tumor organoid cultures from 20 consecutive colorectal carcinoma (CRC) patients. For most, organoids were also generated from adjacent normal tissue.

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Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation.

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