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Primary tumor grafts as advanced models for breast cancer that authentically reflect tumor histopathology, growth, metastasis, and patient outcomes (copy number)

ABSTRACT: Development and pre-clinical testing of new cancer therapies is limited by the scarcity of in vivo models that authentically reproduce tumor growth and metastatic progression. We report new models for breast tumor growth and metastasis, in the form of transplantable tumors derived directly from individuals undergoing treatment for breast cancer. These tumor grafts represent the diversity of human breast cancer and maintain essential features of the original tumors, including metastasis to specific sites. Co-engraftment of primary human mesenchymal stem cells maintains phenotypic stability of the grafts and increases tumor growth by promoting angiogenesis. We also report that tumor engraftment is a prognostic indicator of disease outcome for newly diagnosed women; orthotopic breast tumor grafting marks a step toward individualized models for tumor growth, metastasis, and prognosis. This bank of tumor grafts also serves as a publicly available resource for new models in which to study the biology of breast cancer. Single replicates of genomic DNA from 12 human breast cancer tumors and xenografts of those tumors in immunodeficient mice were hybridized to Affymetrix Human SNP 6.0 genotyping arrays.

ORGANISM(S): Homo sapiens

SUBMITTER: Alana Welm

PROVIDER: E-GEOD-32530 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Patient-derived tumor grafts authentically reflect tumor pathology, growth, metastasis, and disease outcomes (expression)

Project description:Development and pre-clinical testing of new cancer therapies is limited by the scarcity of in vivo models that authentically reproduce tumor growth and metastatic progression. We report new models for breast tumor growth and metastasis, in the form of transplantable tumors derived directly from individuals undergoing treatment for breast cancer. These tumor grafts represent the diversity of human breast cancer and maintain essential features of the original tumors, including metastasis to specific sites. Co-engraftment of primary human mesenchymal stem cells maintains phenotypic stability of the grafts and increases tumor growth by promoting angiogenesis. We also report that tumor engraftment is a prognostic indicator of disease outcome for newly diagnosed women; orthotopic breast tumor grafting marks a step toward individualized models for tumor growth, metastasis, and prognosis. This bank of tumor grafts also serves as a publicly available resource for new models in which to study the biology of breast cancer. Single replicates of total RNA from 12 human breast cancer tumors and xenografts of those tumors in immunodeficient mice were hybridized to Agilent Whole Human Genome expression arrays.

2011-10-22 | E-GEOD-32531 | biostudies-arrayexpress

Primary tumor grafts as advanced models for breast cancer that authentically reflect tumor histopathology, growth, metastasis, and patient outcomes (copy number)

2011-10-23 | GSE32530 | GEO

Patient-derived tumor grafts authentically reflect tumor pathology, growth, metastasis, and disease outcomes (expression)

2011-10-23 | GSE32531 | GEO

Patient-derived tumor grafts authentically reflect tumor pathology, growth, metastasis, and disease outcomes

Project description:This SuperSeries is composed of the following subset Series: GSE32530: Primary tumorgrafts as advanced models for breast cancer that authentically reflect tumor histopathology, growth, metastasis, and patient outcomes (copy number) GSE32531: Patient-derived tumor grafts authentically reflect tumor pathology, growth, metastasis, and disease outcomes (expression) Refer to individual Series

2011-10-22 | E-GEOD-32532 | biostudies-arrayexpress

ATM-inhibitor AZD1390 is a radiosensitizer for breast cancer CNS metastasis

Project description:Purpose: Central nervous system (CNS) metastasis has remained a major source of mortality for breast cancer patients. This is largely driven by the inability of current therapeutics to penetrate the blood brain barrier (BBB) and the lack of preclinical models for testing new therapies. Here we study the efficacy of AZD1390, a BBB penetrating ataxia-telangiectasia mutated (ATM) inhibitor, as a radiosensitizer for breast cancer CNS metastasis treatment. Experimental Design: Three PDX tumors including 2 HER2+ and 1 triple negative breast cancer (TNBC) harboring TP53 mutations, were implanted subcutaneously in the flank of mice to assess tumor growth inhibition by AZD1390 combined with radiation. Animal survival was further assessed by implanting the best responding PDX model orthotopically in the brain. Results: Pretreatment with AZD1390 followed by radiation therapy inhibited growth of PDX tumors implanted in the flank, and improved survival in orthotopic models with average survival 222 days compared to 123 days in controls. Adjuvant administration of AZD1390 had no further benefits. While the combination therapy resulted in sustained tumor inhibition, sporadic regrowth was observed in in some mice 50-100 days post-treatment in all models. Gene expression analysis comparing these tumors with complete responders demonstrated changes in upregulation of multiple oncogenic proteins, which are potential drivers of tumor growth after treatment. Conclusions: Our results demonstrate that AZD1390 effectively sensitizes breast cancer CNS metastasis to radiation therapy in TP53 mutant tumors. This study demonstrates the potential of using AZD1390 as a novel therapeutic agent for patients with breast cancer CNS metastasis.

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Homo sapiens

Project description:Primary tumor grafts as advanced models for breast cancer that authentically reflect tumor histopathology, growth, metastasis, and patient outcomes (copy number)

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Gene expression profiling of FGFR1 KO mice

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CaMKK2 in myeloid cells is a key regulator of the immune suppressive microenvironment in breast cancer

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2019-06-16 | GSE106357 | GEO

Circulating Tumor Cell Clusters are Oligoclonal Precursors of Breast Cancer Metastasis

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