Quantitative optical imaging of primary tumor organoid metabolism predicts drug response in breast cancer

Alex J. Walsh, Rebecca S. Cook, Melinda E. Sanders, Luigi Aurisicchio, Gennaro Ciliberto, Carlos L. Arteaga, Melissa C. Skala

Research output: Contribution to journalArticle

134 Scopus citations

Abstract

There is a need for technologies to predict the efficacy of cancer treatment in individual patients. Here, we show that optical metabolic imaging of organoids derived from primary tumors can predict the therapeutic response of xenografts and measure antitumor drug responses in human tumor-derived organoids. Optical metabolic imaging quantifies the fluorescence intensity and lifetime of NADH and FAD, coenzymes of metabolism. As early as 24 hours after treatment with clinically relevant anticancer drugs, the optical metabolic imaging index of responsive organoids decreased (P < 0.001) and was further reduced when effective therapies were combined (P < 5 ×10<-6<), with no change in drug-resistant organoids. Drug response in xenograft-derived organoids was validated with tumor growth measurements in vivo and staining for proliferation and apoptosis. Heterogeneous cellular responses to drug treatment were also resolved in organoids. Optical metabolic imaging shows potential as a high-throughput screen to test the efficacy of a panel of drugs to select optimal drug combinations.

Original languageEnglish (US)
Pages (from-to)5184-5194
Number of pages11
JournalCancer research
Volume74
Issue number18
DOIs
StatePublished - Aug 6 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Walsh, A. J., Cook, R. S., Sanders, M. E., Aurisicchio, L., Ciliberto, G., Arteaga, C. L., & Skala, M. C. (2014). Quantitative optical imaging of primary tumor organoid metabolism predicts drug response in breast cancer. Cancer research, 74(18), 5184-5194. https://doi.org/10.1158/0008-5472.CAN-14-0663