Patient-Derived Organoids from Locally Advanced Gastric Adenocarcinomas Can Predict Resistance to Neoadjuvant Chemotherapy.

J Gastrointest Surg

Department of Surgery, Columbia University Irving Medical Center, Milstein Hospital Building 7-002, 177 Fort Washington Avenue, New York, NY, 10032, USA.

Published: April 2023

Background: Patients (pts) with locally advanced gastric adenocarcinoma (LAGA) often receive neoadjuvant chemotherapy. A minority of patients do not respond to chemotherapy and thus may benefit from upfront surgery. Patient-derived organoids (PDOs) are an in vitro model that may mimic the chemotherapy response of the original tumors.

Methods: PDOs were generated from endoscopic biopsies of LAGAs prior to the initiation of chemotherapy and treated with the two chemotherapy regimens: FLOT and FOLFOX. Cell proliferation was assayed after 3-6 days. Following chemotherapy, pts underwent surgical resection, and percent pathological necrosis was determined.

Results: Successful PDOs were obtained from 13 of 24 (54%) LAGAs. Failure to generate PDOs were due to contamination (n = 3, 13%), early senescence (n = 3, 13%), and late senescence (n = 5, 21%). By H&E staining, there were significant similarities in tumor morphology and high concordance in immunohistochemical expression of 6 markers between tumors and derived PDOs. Four of 13 pts with successful PDOs did not undergo chemotherapy and surgery. For the remaining 9 pts, percent necrosis in resected tumors was ≤ 50% in 2 pts. The corresponding PDOs from these 2 pts were clearly chemoresistant outliers. The Pearson correlation coefficient between chemosensitivity of PDOs to FOLFOX (n = 2) or FLOT (n = 7) and percent tumor necrosis in resected tumors was 0.87 (p = 0.003).

Conclusions: PDOs from pts with LAGAs in many respects mimic the original tumors from which they are derived and may be used to predict resistance to neoadjuvant chemotherapy.

Synopsis: Patient-derived organoids (PDOs) can serve as personalized in vitro models of patient tumors. In this study, PDOs from locally advanced gastric cancers were able to reliably predict resistance to neoadjuvant chemotherapy.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11605-022-05568-7DOI Listing

Publication Analysis

Top Keywords

patient-derived organoids
12
locally advanced
12
advanced gastric
12
predict resistance
12
resistance neoadjuvant
12
neoadjuvant chemotherapy
12
pdos pts
12
pdos
11
chemotherapy
9
organoids pdos
8

Similar Publications

Establishment and Characterization of Patient-Derived Oral Cancer Organoids.

Methods Mol Biol

January 2025

Mildred Scheel Early Career Centre (MSNZ) for Cancer Research, University Hospital Würzburg, IZKF/MSNZ, Würzburg, Germany.

Oral squamous cell carcinoma (OSCC) is the most common form of head and neck cancer. The current standard for treating primary OSCC is surgical resection combined with radiotherapy and chemotherapy. Despite improved therapeutic strategies, OSCC has high rates of metastasis and mortality, with one in two patients dying of the disease.

View Article and Find Full Text PDF

Protocol for generating a pancreatic cancer organoid associated with heterogeneous tumor microenvironment.

STAR Protoc

January 2025

Division of Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-0071, Japan; Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan; Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan.

Pancreatic ductal adenocarcinoma (PDAC) organoids that simulate the tumor microenvironment (TME) are an effective tool to identify how TME affects PDAC malignancy. We present a protocol for generating a fused pancreatic cancer organoid (FPCO) that partly reproduces the TME, including heterogeneous cancer-associated fibroblasts (CAFs), using patient-derived PDAC cells and human-induced pluripotent cell-derived endothelial and mesenchymal cells. We also describe the procedure for analyzing FPCO characteristics.

View Article and Find Full Text PDF

Inflammatory bowel disease (IBD) is a chronic, relapsing inflammation disorder of the gastrointestinal tract characterized by disrupted intestinal epithelial barrier function. Despite advances in treatment, including biological agents, achieving sustained remission remains challenging for many patients with IBD. This highlights the urgent need for novel therapeutic strategies.

View Article and Find Full Text PDF

Gliomas are a group of primary brain tumors characterized by their aggressive nature and resistance to treatment. Infiltration of surrounding normal tissues limits surgical approaches, wide inter- and intratumor heterogeneity hinders the development of universal therapeutics, and the presence of the blood-brain barrier reduces the efficiency of their delivery. As a result, patients diagnosed with gliomas often face a poor prognosis and low survival rates.

View Article and Find Full Text PDF

Precision Treatment of Metachronous Multiple Primary Malignancies Based on Constructing Patient Tumor-Derived Organoids.

Biomedicines

November 2024

Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.

When a patient has two or more primary tumors, excluding the possibility of diffuse, recurrent, or metastatic, they can be defined as having multiple primary malignant neoplasms (MPMNs). Moreover, cases of three primary urinary tract tumors are very rare. Here, we reported a patient of MPMNs with four primary tumors, including three urinary tract cancers (renal cancer, prostate cancer, and bladder cancer) and lung cancer.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!