Dataset Information

Organoid Sensitivity Correlates with Therapeutic Response in Patients with Pancreatic Cancer.

ABSTRACT:

Purpose

Pancreatic ductal adenocarcinoma (PDAC) remains a significant health issue. For most patients, there are no options for targeted therapy, and existing treatments are limited by toxicity. The HOPE trial (Harnessing Organoids for PErsonalized Therapy) was a pilot feasibility trial aiming to prospectively generate patient-derived organoids (PDO) from patients with PDAC and test their drug sensitivity and correlation with clinical outcomes.

Experimental design

PDOs were established from a heterogeneous population of patients with PDAC including both basal and classical PDAC subtypes.

Results

A method for classifying PDOs as sensitive or resistant to chemotherapy regimens was developed to predict the clinical outcome of patients. Drug sensitivity testing on PDOs correlated with clinical responses to treatment in individual patients.

Conclusions

These data support the investigation of PDOs to guide treatment in prospective interventional trials in PDAC.

SUBMITTER: Grossman JE

PROVIDER: S-EPMC8866201 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Organoid Sensitivity Correlates with Therapeutic Response in Patients with Pancreatic Cancer.

Grossman Joseph E JE Muthuswamy Lakshmi L Huang Ling L Akshinthala Dipikaa D Perea Sofia S Gonzalez Raul S RS Tsai Leo L LL Cohen Jonah J Bockorny Bruno B Bullock Andrea J AJ Schlechter Benjamin B Peters Mary Linton B MLB Conahan Catherine C Narasimhan Supraja S Lim Christine C Davis Roger B RB Besaw Robert R Sawhney Mandeep S MS Pleskow Douglas D Berzin Tyler M TM Smith Martin M Kent Tara S TS Callery Mark M Muthuswamy Senthil K SK Hidalgo Manuel M

Clinical cancer research : an official journal of the American Association for Cancer Research 20220201 4

<h4>Purpose</h4>Pancreatic ductal adenocarcinoma (PDAC) remains a significant health issue. For most patients, there are no options for targeted therapy, and existing treatments are limited by toxicity. The HOPE trial (Harnessing Organoids for PErsonalized Therapy) was a pilot feasibility trial aiming to prospectively generate patient-derived organoids (PDO) from patients with PDAC and test their drug sensitivity and correlation with clinical outcomes.<h4>Experimental design</h4>PDOs were establ ...[more]

PMID: 34789479

Similar Datasets

Project description:PurposePatient-derived organoids (PDO) are a promising technology to support precision medicine initiatives for patients with pancreatic ductal adenocarcinoma (PDAC). PDOs may improve clinical next-generation sequencing (NGS) and enable rapid ex vivo chemotherapeutic screening (pharmacotyping).Experimental designPDOs were derived from tissues obtained during surgical resection and endoscopic biopsies and studied with NGS and pharmacotyping. PDO-specific pharmacotype is assessed prospectively as a predictive biomarker of clinical therapeutic response by leveraging data from a randomized controlled clinical trial.ResultsClinical sequencing pipelines often fail to detect PDAC-associated somatic mutations in surgical specimens that demonstrate a good pathologic response to previously administered chemotherapy. Sequencing the PDOs derived from these surgical specimens, after biomass expansion, improves the detection of somatic mutations and enables quantification of copy number variants. The detection of clinically relevant mutations and structural variants is improved following PDO biomass expansion. On clinical trial, PDOs were derived from biopsies of treatment-naïve patients prior to treatment with FOLFIRINOX (FFX). Ex vivo PDO pharmacotyping with FFX components predicted clinical therapeutic response in these patients with borderline resectable or locally advanced PDAC treated in a neoadjuvant or induction paradigm. PDO pharmacotypes suggesting sensitivity to FFX components were associated with longitudinal declines of tumor marker, carbohydrate-antigen 19-9 (CA-19-9), and favorable RECIST imaging response.ConclusionsPDOs established from tissues obtained from patients previously receiving cytotoxic chemotherapies can be accomplished in a clinically certified laboratory. Sequencing PDOs following biomass expansion improves clinical sequencing quality. High in vitro sensitivity to standard-of-care chemotherapeutics predicts good clinical response to systemic chemotherapy in PDAC. See related commentary by Zhang et al., p. 3176.

Dataset Information

Organoid Sensitivity Correlates with Therapeutic Response in Patients with Pancreatic Cancer.

Purpose

Experimental design

Results

Conclusions

Publications

Organoid Sensitivity Correlates with Therapeutic Response in Patients with Pancreatic Cancer.

Similar Datasets

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