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Screening in serum-derived medium reveals differential response to compounds targeting metabolism.
Abbott, Keene L; Ali, Ahmed; Casalena, Dominick; Do, Brian T; Ferreira, Raphael; Cheah, Jaime H; Soule, Christian K; Deik, Amy; Kunchok, Tenzin; Schmidt, Daniel R; Renner, Steffen; Honeder, Sophie E; Wu, Michelle; Chan, Sze Ham; Tseyang, Tenzin; Stoltzfus, Andrew T; Michel, Sarah L J; Greaves, Daniel; Hsu, Peggy P; Ng, Christopher W; Zhang, Chelsea J; Farsidjani, Ali; Kent, Johnathan R; Madariaga, Maria Lucia L; Gramatikov, Iva Monique T; Matheson, Nicholas J; Lewis, Caroline A; Clish, Clary B; Rees, Matthew G; Roth, Jennifer A; Griner, Lesley Mathews; Muir, Alexander; Auld, Douglas S; Vander Heiden, Matthew G.
Afiliação
  • Abbott KL; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Ali A; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Casalena D; Novartis Institute for BioMedical Research, Cambridge, MA 02139, USA.
  • Do BT; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard-MIT Health Sciences and Technology, Cambridge, MA 02139, USA.
  • Ferreira R; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Cheah JH; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Soule CK; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Deik A; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Kunchok T; Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA.
  • Schmidt DR; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
  • Renner S; Novartis Institutes for BioMedical Research, 4056 Basel, Switzerland.
  • Honeder SE; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria.
  • Wu M; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Chan SH; Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA.
  • Tseyang T; Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA.
  • Stoltzfus AT; Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
  • Michel SLJ; Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
  • Greaves D; Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
  • Hsu PP; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Dana-Farber Cancer Institute, Boston, MA 02115, USA; Massachusetts General Hospital Cancer Center, Boston, MA 02113, USA.
  • Ng CW; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Zhang CJ; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Farsidjani A; Novartis Institute for BioMedical Research, Cambridge, MA 02139, USA.
  • Kent JR; Department of Surgery, University of Chicago Medicine, Chicago, IL 60637, USA.
  • Madariaga MLL; Department of Surgery, University of Chicago Medicine, Chicago, IL 60637, USA.
  • Gramatikov IMT; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
  • Matheson NJ; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ,
  • Lewis CA; Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA.
  • Clish CB; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Rees MG; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Roth JA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Griner LM; Novartis Institute for BioMedical Research, Cambridge, MA 02139, USA.
  • Muir A; Ben May Department of Cancer Research, University of Chicago, Chicago, IL 60637, USA.
  • Auld DS; Novartis Institute for BioMedical Research, Cambridge, MA 02139, USA.
  • Vander Heiden MG; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Dana-Farber Cancer Institute, Boston,
Cell Chem Biol ; 30(9): 1156-1168.e7, 2023 09 21.
Article em En | MEDLINE | ID: mdl-37689063
ABSTRACT
A challenge for screening new anticancer drugs is that efficacy in cell culture models is not always predictive of efficacy in patients. One limitation of standard cell culture is a reliance on non-physiological nutrient levels, which can influence cell metabolism and drug sensitivity. A general assessment of how physiological nutrients affect cancer cell response to small molecule therapies is lacking. To address this, we developed a serum-derived culture medium that supports the proliferation of diverse cancer cell lines and is amenable to high-throughput screening. We screened several small molecule libraries and found that compounds targeting metabolic enzymes were differentially effective in standard compared to serum-derived medium. We exploited the differences in nutrient levels between each medium to understand why medium conditions affected the response of cells to some compounds, illustrating how this approach can be used to screen potential therapeutics and understand how their efficacy is modified by available nutrients.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Técnicas de Cultura de Células / Ensaios de Triagem em Larga Escala Tipo de estudo: Diagnostic_studies / Prognostic_studies / Screening_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Técnicas de Cultura de Células / Ensaios de Triagem em Larga Escala Tipo de estudo: Diagnostic_studies / Prognostic_studies / Screening_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article