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. |
---|---|
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) |
References: | Cancer Chemother Pharmacol. 2010 May;65(6):1165-72. (PMID: 19789873) Drug Metab Pharmacokinet. 2009;24(4):300-7. (PMID: 19745557) Cancer Cell. 2017 Jul 10;32(1):9-25. (PMID: 28697345) Elife. 2017 Aug 15;6:. (PMID: 28826492) Invest New Drugs. 2008 Feb;26(1):45-51. (PMID: 17924057) Cancer Res. 1981 Apr;41(4):1324-8. (PMID: 7214322) Elife. 2020 Jul 10;9:. (PMID: 32648540) Neurology. 1966 Nov;16(11):1064-70. (PMID: 5950917) Cancer Res. 1987 Sep 15;47(18):4924-31. (PMID: 3621184) Cell Metab. 2019 May 7;29(5):1166-1181.e6. (PMID: 30799286) Nat Commun. 2017 Jul 07;8:16031. (PMID: 28685754) Sci Adv. 2019 Jan 02;5(1):eaau7314. (PMID: 30613774) Cell. 2015 Sep 10;162(6):1229-41. (PMID: 26321679) Eur J Cancer. 2005 Mar;41(5):702-7. (PMID: 15763645) Nat Commun. 2017 Jul 03;8:15965. (PMID: 28671190) Sci Signal. 2020 Mar 24;13(624):. (PMID: 32209698) Cell Metab. 2016 Nov 8;24(5):716-727. (PMID: 27746050) Nat Metab. 2021 Nov;3(11):1512-1520. (PMID: 34799699) Nature. 2014 Apr 3;508(7494):108-12. (PMID: 24670634) Sci Transl Med. 2018 May 23;10(442):. (PMID: 29794058) Cell Metab. 2015 Jul 7;22(1):31-53. (PMID: 26118927) Nat Biotechnol. 2016 Apr;34(4):419-23. (PMID: 26928769) Cell Metab. 2016 Mar 8;23(3):517-28. (PMID: 26853747) Nat Commun. 2017 Jan 10;8:13989. (PMID: 28071763) Mol Cancer Ther. 2020 Feb;19(2):397-408. (PMID: 31594823) PLoS One. 2011 Feb 16;6(2):e16957. (PMID: 21359215) Clin Cancer Res. 2002 Sep;8(9):2843-50. (PMID: 12231525) Nat Cell Biol. 2015 Dec;17(12):1556-68. (PMID: 26595383) Cell. 2017 Feb 9;168(4):657-669. (PMID: 28187287) Sci Signal. 2021 Jun 08;14(686):. (PMID: 34103421) Cell Chem Biol. 2017 Sep 21;24(9):1161-1180. (PMID: 28938091) Nature. 2021 Nov;599(7884):302-307. (PMID: 34671163) Sci Adv. 2022 Jan 21;8(3):eabg6383. (PMID: 35061540) Nat Rev Drug Discov. 2011 Jun 24;10(7):507-19. (PMID: 21701501) In Vitro Cell Dev Biol. 1988 Sep;24(9):878-84. (PMID: 3170445) Front Endocrinol (Lausanne). 2017 Sep 29;8:261. (PMID: 29085336) Cell. 2016 Sep 22;167(1):171-186.e15. (PMID: 27641501) Elife. 2019 Apr 16;8:. (PMID: 30990168) Mol Cell Biol. 2009 Nov;29(21):5872-88. (PMID: 19703994) Cell. 2015 Jul 16;162(2):259-270. (PMID: 26144316) Nat Metab. 2020 Dec;2(12):1401-1412. (PMID: 33257855) Nat Rev Mol Cell Biol. 2021 Apr;22(4):266-282. (PMID: 33495651) Cell. 2017 Apr 06;169(2):258-272.e17. (PMID: 28388410) Scand J Clin Lab Invest. 1983 Oct;43(6):503-12. (PMID: 6419345) Nat Rev Drug Discov. 2017 Aug;16(8):531-543. (PMID: 28685762) Cancer Res. 1962 Jun;22:581-8. (PMID: 13874819) Cell. 2015 Sep 10;162(6):1217-28. (PMID: 26321681) Nucleic Acids Res. 2022 Jan 7;50(D1):D622-D631. (PMID: 34986597) Cell Metab. 2021 Jun 1;33(6):1248-1263.e9. (PMID: 33651980) Cell Chem Biol. 2022 Nov 17;29(11):1588-1600.e7. (PMID: 36306785) Langmuir. 2008 Aug 19;24(16):8402-4. (PMID: 18627191) Nat Cell Biol. 2018 Jul;20(7):782-788. (PMID: 29941931) Nature. 2017 Jul 27;547(7664):453-457. (PMID: 28678785) Nat Rev Cancer. 2019 Nov;19(11):651-661. (PMID: 31530936) Nat Metab. 2021 Nov;3(11):1500-1511. (PMID: 34799701) Trends Cell Biol. 2017 Nov;27(11):863-875. (PMID: 28734735) Cancer Res. 1964 Jun;24:780-94. (PMID: 14190544) Cell Chem Biol. 2020 Sep 17;27(9):1124-1129. (PMID: 32707038) Mol Cancer Ther. 2018 Sep;17(9):1824-1832. (PMID: 30181331) Pharmacol Ther. 2015 Jul;151:16-31. (PMID: 25709099) Cell Metab. 2022 Sep 6;34(9):1298-1311.e6. (PMID: 35981545) |
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 |
---|