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

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, func...

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Bibliographic Details
Published in:	Clinical cancer research Vol. 26; no. 14; pp. 3662 - 3670
Main Authors:	Narasimhan, Vignesh, Wright, Josephine A, Churchill, Michael, Wang, Tongtong, Rosati, Rachele, Lannagan, Tamsin R M, Vrbanac, Laura, Richardson, Anne B, Kobayashi, Hiroki, Price, Timothy, Tye, Gayle X Y, Marker, Julie, Hewett, Peter J, Flood, Michael P, Pereira, Shalini, Whitney, G Adam, Michael, Michael, Tie, Jeanne, Mukherjee, Siddhartha, Grandori, Carla, Heriot, Alexander G, Worthley, Daniel L, Ramsay, Robert G, Woods, Susan L
Format:	Journal Article
Language:	English
Published:	United States 15-07-2020
Online Access:	Get full text
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Summary:	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. CRPM organoids (peritonoids) isolated from patients underwent parallel next-generation sequencing and medium-throughput drug panel testing 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. 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. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author contributions: VN, JAW, RR, TRML, LV did the experiments. VN, JAW, MC, TW, HK, AR, GXYT, SP, AW, SLW collected and analysed data. RGR, DLW, SM, CG, AH, MM, SLW provided support and reagents. AH, MM, JT, PH, TP, VN were involved in patient care. JM provided consumer input. SLW, VN, DLW, RGR, MC, CG wrote the manuscript. All authors contributed to and approved the final manuscript.
ISSN:	1078-0432 1557-3265
DOI:	10.1158/1078-0432.ccr-20-0073