Screening in serum-derived medium reveals differential response to compounds targeting metabolism.
Keene L Abbott, Ahmed Ali, Dominick Casalena, Brian T Do, Raphael Ferreira, Jaime H Cheah, Christian K Soule, Amy Deik, Tenzin Kunchok, Daniel R Schmidt, Steffen Renner, Sophie E Honeder, Michelle Wu, Sze Ham Chan, Tenzin Tseyang, Andrew T Stoltzfus, Sarah L J Michel, Daniel Greaves, Peggy P Hsu, Christopher W Ng, Chelsea J Zhang, Ali Farsidjani, Johnathan R Kent, Maria Lucia L Madariaga, Iva Monique T Gramatikov, Nicholas J Matheson, Caroline A Lewis, Clary B Clish, Matthew G Rees, Jennifer A Roth, Lesley Mathews Griner, Alexander Muir, Douglas S Auld, Matthew G Vander Heiden
Author Information
Keene L Abbott: 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.
Ahmed Ali: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Dominick Casalena: Novartis Institute for BioMedical Research, Cambridge, MA 02139, USA.
Brian T Do: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard-MIT Health Sciences and Technology, Cambridge, MA 02139, USA.
Raphael Ferreira: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Jaime H Cheah: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Christian K Soule: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Amy Deik: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Tenzin Kunchok: Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA.
Daniel R Schmidt: 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.
Steffen Renner: Novartis Institutes for BioMedical Research, 4056 Basel, Switzerland.
Sophie E Honeder: 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.
Michelle Wu: 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.
Sze Ham Chan: Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA.
Tenzin Tseyang: Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA.
Andrew T Stoltzfus: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
Sarah L J Michel: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
Daniel Greaves: Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
Peggy P Hsu: 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.
Christopher W Ng: 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.
Chelsea J Zhang: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Ali Farsidjani: Novartis Institute for BioMedical Research, Cambridge, MA 02139, USA.
Johnathan R Kent: Department of Surgery, University of Chicago Medicine, Chicago, IL 60637, USA.
Maria Lucia L Madariaga: Department of Surgery, University of Chicago Medicine, Chicago, IL 60637, USA.
Iva Monique T Gramatikov: 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.
Nicholas J Matheson: 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.
Caroline A Lewis: Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA.
Clary B Clish: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Matthew G Rees: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jennifer A Roth: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Lesley Mathews Griner: Novartis Institute for BioMedical Research, Cambridge, MA 02139, USA.
Alexander Muir: Ben May Department of Cancer Research, University of Chicago, Chicago, IL 60637, USA.
Douglas S Auld: Novartis Institute for BioMedical Research, Cambridge, MA 02139, USA.
Matthew G Vander Heiden: 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. Electronic address: mvh@mit.edu.
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.
