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Cancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility.

Circulating tumor cells (CTCs) are present at low concentrations in the peripheral blood of patients with solid tumors. It has been proposed that the isolation, ex vivo culture, and characterization of CTCs may provide an opportunity to noninvasively monitor the changing patterns of drug susceptibil... Full description

Journal Title: Science (New York N.Y.), July 11, 2014, Vol.345(6193), pp.216-220
Main Author: Yu, Min
Other Authors: Bardia, Aditya , Aceto, Nicola , Bersani, Francesca , Madden, Marissa W , Donaldson, Maria C , Desai, Rushil , Zhu, Huili , Comaills, Valentine , Zheng, Zongli , Wittner, Ben S , Stojanov, Petar , Brachtel, Elena , Sgroi, Dennis , Kapur, Ravi , Shioda, Toshihiro , Ting, David T , Ramaswamy, Sridhar , Getz, Gad , Iafrate
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1095-9203 ; DOI: 10.1126/science.1253533
Link: http://search.proquest.com/docview/1544737785/?pq-origsite=primo
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title: Cancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility.
format: Article
creator:
  • Yu, Min
  • Bardia, Aditya
  • Aceto, Nicola
  • Bersani, Francesca
  • Madden, Marissa W
  • Donaldson, Maria C
  • Desai, Rushil
  • Zhu, Huili
  • Comaills, Valentine
  • Zheng, Zongli
  • Wittner, Ben S
  • Stojanov, Petar
  • Brachtel, Elena
  • Sgroi, Dennis
  • Kapur, Ravi
  • Shioda, Toshihiro
  • Ting, David T
  • Ramaswamy, Sridhar
  • Getz, Gad
  • Iafrate
subjects:
  • Animals–Pharmacology
  • Antineoplastic Agents–Therapeutic Use
  • Breast Neoplasms–Drug Therapy
  • Cell Culture Techniques–Genetics
  • Cell Separation–Genetics
  • Class I Phosphatidylinositol 3-Kinases–Methods
  • Culture–Genetics
  • Drug Resistance, Neoplasm–Methods
  • Drug Screening Assays, Antitumor–Drug Effects
  • Estrogen Receptor Alpha–Metabolism
  • Female–Genetics
  • Gene Frequency–Genetics
  • Humans–Genetics
  • Mice–Genetics
  • Microfluidics–Genetics
  • Molecular Targeted Therapy–Genetics
  • Mutation–Genetics
  • Neoplastic Cells, Circulating–Genetics
  • Phosphatidylinositol 3-Kinases–Genetics
  • Sequence Analysis, DNA
ispartof: Science (New York, N.Y.), July 11, 2014, Vol.345(6193), pp.216-220
description: Circulating tumor cells (CTCs) are present at low concentrations in the peripheral blood of patients with solid tumors. It has been proposed that the isolation, ex vivo culture, and characterization of CTCs may provide an opportunity to noninvasively monitor the changing patterns of drug susceptibility in individual patients as their tumors acquire new mutations. In a proof-of-concept study, we established CTC cultures from six patients with estrogen receptor-positive breast cancer. Three of five CTC lines tested were tumorigenic in mice. Genome sequencing of the CTC lines revealed preexisting mutations in the PIK3CA gene and newly acquired mutations in the estrogen receptor gene (ESR1), PIK3CA gene, and fibroblast growth factor receptor gene (FGFR2), among others. Drug sensitivity testing of CTC lines with multiple mutations revealed potential new therapeutic targets. With optimization of CTC culture conditions, this strategy may help identify the best therapies for individual cancer patients over the course of their disease. 10.1126/science.1253533
language: eng
source:
identifier: E-ISSN: 1095-9203 ; DOI: 10.1126/science.1253533
fulltext: no_fulltext
issn:
  • 10959203
  • 1095-9203
url: Link


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titleCancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility.
creatorYu, Min ; Bardia, Aditya ; Aceto, Nicola ; Bersani, Francesca ; Madden, Marissa W ; Donaldson, Maria C ; Desai, Rushil ; Zhu, Huili ; Comaills, Valentine ; Zheng, Zongli ; Wittner, Ben S ; Stojanov, Petar ; Brachtel, Elena ; Sgroi, Dennis ; Kapur, Ravi ; Shioda, Toshihiro ; Ting, David T ; Ramaswamy, Sridhar ; Getz, Gad ; Iafrate
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ispartofScience (New York, N.Y.), July 11, 2014, Vol.345(6193), pp.216-220
identifierE-ISSN: 1095-9203 ; DOI: 10.1126/science.1253533
subjectAnimals–Pharmacology ; Antineoplastic Agents–Therapeutic Use ; Breast Neoplasms–Drug Therapy ; Cell Culture Techniques–Genetics ; Cell Separation–Genetics ; Class I Phosphatidylinositol 3-Kinases–Methods ; Culture–Genetics ; Drug Resistance, Neoplasm–Methods ; Drug Screening Assays, Antitumor–Drug Effects ; Estrogen Receptor Alpha–Metabolism ; Female–Genetics ; Gene Frequency–Genetics ; Humans–Genetics ; Mice–Genetics ; Microfluidics–Genetics ; Molecular Targeted Therapy–Genetics ; Mutation–Genetics ; Neoplastic Cells, Circulating–Genetics ; Phosphatidylinositol 3-Kinases–Genetics ; Sequence Analysis, DNA
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descriptionCirculating tumor cells (CTCs) are present at low concentrations in the peripheral blood of patients with solid tumors. It has been proposed that the isolation, ex vivo culture, and characterization of CTCs may provide an opportunity to noninvasively monitor the changing patterns of drug susceptibility in individual patients as their tumors acquire new mutations. In a proof-of-concept study, we established CTC cultures from six patients with estrogen receptor-positive breast cancer. Three of five CTC lines tested were tumorigenic in mice. Genome sequencing of the CTC lines revealed preexisting mutations in the PIK3CA gene and newly acquired mutations in the estrogen receptor gene (ESR1), PIK3CA gene, and fibroblast growth factor receptor gene (FGFR2), among others. Drug sensitivity testing of CTC lines with multiple mutations revealed potential new therapeutic targets. With optimization of CTC culture conditions, this strategy may help identify the best therapies for individual cancer patients over the course of their disease. 10.1126/science.1253533
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titleCancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility.
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titleCancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility.
authorYu, Min ; Bardia, Aditya ; Aceto, Nicola ; Bersani, Francesca ; Madden, Marissa W ; Donaldson, Maria C ; Desai, Rushil ; Zhu, Huili ; Comaills, Valentine ; Zheng, Zongli ; Wittner, Ben S ; Stojanov, Petar ; Brachtel, Elena ; Sgroi, Dennis ; Kapur, Ravi ; Shioda, Toshihiro ; Ting, David T ; Ramaswamy, Sridhar ; Getz, Gad ; Iafrate
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5Class I Phosphatidylinositol 3-Kinases–Methods
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10Female–Genetics
11Gene Frequency–Genetics
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13Mice–Genetics
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17Neoplastic Cells, Circulating–Genetics
18Phosphatidylinositol 3-Kinases–Genetics
19Sequence Analysis, DNA
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atitleCancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility.
jtitleScience (New York, N.Y.)
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