Medium-throughput drug screening of patient-derived organoids from colorectal peritoneal metastases to direct personalized therapy
- Narasimhan, V; Wright, JA; Churchill, M; Wang, T; Rosati, R; Lannagan, TRM; Vrbanac, L; Richardson, AB; Kobayashi, H; Price, T; Tye, GXY; Marker, J; Hewett, PJ; Flood, MP; Pereira, S; Whitney, GA; Michael, M; Tie, J; Mukherjee, S; Grandori, C; Heriot, AG; Worthley, DL; Ramsay, RG; Woods, SL;
Publication Year 2020-07-15, Volume 26, Issue #14, Page 3662-3670
- Journal Title
- Clinical Cancer Research
- Publication Type
- Journal Article
- 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.
- WEHI Research Division(s)
- Personalised Oncology
- PubMed ID
- Publisher's Version
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2020-08-05 11:11:26Last Modified: 2020-08-05 04:33:41