Metabolic Heterogeneity in Patient Tumor-Derived Organoids by Primary Site and Drug Treatment

Joe T. Sharick, Christine M. Walsh, Carley M. Sprackling, Cheri A. Pasch, Dan L. Pham, Karla Esbona, Alka Choudhary, Rebeca Garcia-Valera, Mark E. Burkard, Stephanie M. McGregor, Kristina A. Matkowskyj, Alexander A. Parikh, Ingrid M. Meszoely, Mark C. Kelley, Susan Tsai, Dustin A. Deming, Melissa C. Skala

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

New tools are needed to match cancer patients with effective treatments. Patient-derived organoids offer a high-throughput platform to personalize treatments and discover novel therapies. Currently, methods to evaluate drug response in organoids are limited because they overlook cellular heterogeneity. In this study, non-invasive optical metabolic imaging (OMI) of cellular heterogeneity was characterized in breast cancer (BC) and pancreatic cancer (PC) patient-derived organoids. Baseline heterogeneity was analyzed for each patient, demonstrating that single-cell techniques, such as OMI, are required to capture the complete picture of heterogeneity present in a sample. Treatment-induced changes in heterogeneity were also analyzed, further demonstrating that these measurements greatly complement current techniques that only gauge average cellular response. Finally, OMI of cellular heterogeneity in organoids was evaluated as a predictor of clinical treatment response for the first time. Organoids were treated with the same drugs as the patient's prescribed regimen, and OMI measurements of heterogeneity were compared to patient outcome. OMI distinguished subpopulations of cells with divergent and dynamic responses to treatment in living organoids without the use of labels or dyes. OMI of organoids agreed with long-term therapeutic response in patients. With these capabilities, OMI could serve as a sensitive high-throughput tool to identify optimal therapies for individual patients, and to develop new effective therapies that address cellular heterogeneity in cancer.

Original languageEnglish (US)
Article number553
JournalFrontiers in Oncology
Volume10
DOIs
StatePublished - May 15 2020
Externally publishedYes

Keywords

  • breast cancer
  • cellular metabolism
  • heterogeneity
  • optical metabolic imaging
  • organoid
  • pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Metabolic Heterogeneity in Patient Tumor-Derived Organoids by Primary Site and Drug Treatment'. Together they form a unique fingerprint.

Cite this