Organoid Level Assessments of Human Primary and Metastatic Colorectal Cancer-Derived Organoids Predict Response to Chemotherapy and Chemoradiation

  • Cancers (Basel). 2026 May 13;18(10):1587. doi: 10.3390/cancers18101587.
Shirsa Udgata  1 ,  Alexa E Schmitz  1 ,  Amani A Gillette  2 ,  Alexandra G Sorenson  2  3 ,  Jeremiah M Riendeau  3 ,  Rian Engeldinger  1 ,  Jordan N Stoecker  1 ,  Alyssa K Steimle  1 ,  Katherine A Johnson  1  4 ,  Devan Kittelson  5 ,  Alexandra Isaak  2 ,  Jeremy D Kratz  1  4 ,  Evie Carchman  4  6  7 ,  Randall Kimple  4  8 ,  Cheri A Pasch  1  4 ,  Melissa C Skala  2  3 ,  Dustin A Deming  1  4  9
Affiliations
  • 1. Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.
  • 2. Morgridge Institute for Research, Madison, WI 53715, USA.
  • 3. Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA.
  • 4. University of Wisconsin Carbone Cancer Center, Madison, WI 53705, USA.
  • 5. School of Computer, Data, and Information Sciences, University of Wisconsin-Madison, Madison, WI 53705, USA.
  • 6. Department of Surgery, William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA.
  • 7. Department of Surgery, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.
  • 8. Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.
  • 9. McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, Madison, WI 53705, USA.
PMID: 42192947 DOI: 10.3390/cancers18101587
Abstract

Background: Therapies for metastatic colorectal Cancer (CRC) are largely chosen without considering inter-patient heterogeneity, leading to unnecessary side effects without clinical benefit for some patients. Patient-derived Cancer organoids (PDCOs) faithfully recapitulate the morphology and molecular profiles of the primary tumors from which they are derived, making them attractive preclinical models for predicting response to standard therapies, and thus, for use in drug development assays.

Methods: Here, we investigate the hidden subclonal driver mutations in CRC PDCOs and the importance of individual PDCO-level heterogeneity when addressing PDCO treatment responses using changes in diameter and optical redox imaging. PDCO response is then compared to clinical response across a cohort of subjects with CRC receiving chemotherapy and/or chemoradiation.

Results: Change in diameter and optical redox imaging are more sensitive to detecting therapeutic response than endpoint and well-level measurements. These measurements accurately reflect clinical responses to chemotherapy and chemoradiation.

Conclusions: Overall, these studies demonstrate the importance of PDCO-level methods of PDCO assessment and further establish PDCOs as powerful tools for drug response assessment and developmental therapeutic studies.

Keywords
colorectal cancer; optical redox imaging; organoids; patient-derived cancer organoids; preclinical cancer models.
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