Screening in serum-derived medium reveals differential response to compounds targeting metabolism.
| العنوان: | Screening in serum-derived medium reveals differential response to compounds targeting metabolism. |
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| المؤلفون: | 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, 181 Massachusetts Avenue, 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, 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, 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., 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, 181 Massachusetts Avenue, Cambridge, MA 02139, 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, 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, UK., 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, 181 Massachusetts Avenue, Cambridge, MA 02139, USA., Muir A; Ben May Department of Cancer Research, University of Chicago, Chicago, IL, USA., Auld DS; Novartis Institute for BioMedical Research, 181 Massachusetts Avenue, Cambridge, MA 02139, USA., Heiden MGV; 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, MA 02115, USA. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2023 Feb 27. Date of Electronic Publication: 2023 Feb 27. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | A challenge for screening new candidate drugs to treat cancer 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 to propagate cells. Which nutrients are available can influence how cancer cells use metabolism to proliferate and impact sensitivity to some drugs, but a general assessment of how physiological nutrients affect cancer cell response to small molecule therapies is lacking. To enable screening of compounds to determine how the nutrient environment impacts drug efficacy, we developed a serum-derived culture medium that supports the proliferation of diverse cancer cell lines and is amenable to high-throughput screening. We used this system to screen several small molecule libraries and found that compounds targeting metabolic enzymes were enriched as having differential efficacy 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. |
| التعليقات: | Update in: Cell Chem Biol. 2023 Aug 31;:. (PMID: 37689063) |
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| معلومات مُعتمدة: | KL2 TR002542 United States TR NCATS NIH HHS; T32 GM007753 United States GM NIGMS NIH HHS; R35 CA242379 United States CA NCI NIH HHS; T32 CA071345 United States CA NCI NIH HHS; P50 CA090381 United States CA NCI NIH HHS; F30 HL156404 United States HL NHLBI NIH HHS; T32 GM007287 United States GM NIGMS NIH HHS; F31 CA271787 United States CA NCI NIH HHS; United Kingdom WT_ Wellcome Trust |
| تواريخ الأحداث: | Date Created: 20230313 Latest Revision: 20230922 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC10002634 |
| DOI: | 10.1101/2023.02.25.529972 |
| PMID: | 36909640 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2023.02.25.529972 |
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