Medium-throughput Drug Screening of Patient-derived Organoids from Colorectal Peritoneal Metastases to Direct Personalized Therapy

Vignesh Narasimhan, Josephine A. Wright, Michael Churchill, Tongtong Wang, Rachele Rosati, Tamsin R.M. Lannagan, Laura Vrbanac, Anne B. Richardson, Hiroki Kobayashi, Timothy Price, Gayle X.Y. Tye, Julie Marker, Peter J. Hewett, Michael P. Flood, Shalini Pereira, G. Adam Whitney, Michael Michael, Jeanne Tie, Siddhartha Mukherjee, Carla GrandoriAlexander G. Heriot, Daniel L. Worthley, Robert G. Ramsay, Susan L. Woods

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)

Abstract

PURPOSE: Patients with colorectal cancer with peritoneal metastases (CRPMs) have limited treatment options and the lowest colorectal cancer survival rates. We aimed to determine whether organoid testing could help guide precision treatment for patients with CRPMs, as the clinical utility of prospective, functional drug screening including nonstandard agents is unknown.

EXPERIMENTAL DESIGN: CRPM organoids (peritonoids) isolated from patients underwent parallel next-generation sequencing and medium-throughput drug panel testing ex vivo to identify specific drug sensitivities for each patient. We measured the utility of such a service including: success of peritonoid generation, time to cultivate peritonoids, reproducibility of the medium-throughput drug testing, and documented changes to clinical therapy as a result of the testing.

RESULTS: Peritonoids were successfully generated and validated from 68% (19/28) of patients undergoing standard care. Genomic and drug profiling was completed within 8 weeks and a formal report ranking drug sensitivities was provided to the medical oncology team upon failure of standard care treatment. This resulted in a treatment change for two patients, one of whom had a partial response despite previously progressing on multiple rounds of standard care chemotherapy. The barrier to implementing this technology in Australia is the need for drug access and funding for off-label indications.

CONCLUSIONS: Our approach is feasible, reproducible, and can guide novel therapeutic choices in this poor prognosis cohort, where new treatment options are urgently needed. This platform is relevant to many solid organ malignancies.

Original languageEnglish
Pages (from-to)3662-3670
Number of pages9
JournalClinical Cancer Research
Volume26
Issue number14
Early online date6 May 2020
DOIs
Publication statusPublished or Issued - 15 Jul 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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