Patient-Derived Organoids from Multiple Colorectal Cancer Liver Metastases Reveal Moderate Intra-patient Pharmacotranscriptomic Heterogeneity

Bruun, Jarle; Kryeziu, Kushtrim; Eide, Peter W.; Moosavi, Seyed H.; Eilertsen, Ina A.; Langerud, Jonas; Røsok, Bård I.; Totland, Max Z.; Brunsell, Tuva H.; Pellinen, Teijo; Saarela, Jani; Bergsland, Christian H.; Pálmer, Héctor G.; Brudvik, Kristoffer Watten; Guren, Tormod Kyrre; Dienstmann, Rodrigo; Guren, Marianne Grønlie; Nesbakken, Arild; Bjørnbeth, Bjørn Atle; Sveen, Anita; Lothe, Ragnhild

doi:10.1158/1078-0432.ccr-19-3637

Cited by 77 publications

(85 citation statements)

References 56 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The authors used 39 tissue metastases from 22 patients. After analysis, it was possible to predict the most appropriate drug and assess the sensitivity to the drug; for example, organoids of patients 25 and 29 were sensitive to drugs in phase 2/3 clinical trials [ 134 ].…”

Section: Spheroids and Organoids For Personalized Medicinementioning

confidence: 99%

Promising Applications of Tumor Spheroids and Organoids for Personalized Medicine

Gilazieva

Ponomarev

Rutland

et al. 2020

Cancers

View full text Add to dashboard Cite

One of the promising directions in personalized medicine is the use of three-dimensional (3D) tumor models such as spheroids and organoids. Spheroids and organoids are three-dimensional cultures of tumor cells that can be obtained from patient tissue and, using high-throughput personalized medicine methods, provide a suitable therapy for that patient. These 3D models can be obtained from most types of tumors, which provides opportunities for the creation of biobanks with appropriate patient materials that can be used to screen drugs and facilitate the development of therapeutic agents. It should be noted that the use of spheroids and organoids would expand the understanding of tumor biology and its microenvironment, help develop new in vitro platforms for drug testing and create new therapeutic strategies. In this review, we discuss 3D tumor spheroid and organoid models, their advantages and disadvantages, and evaluate their promising use in personalized medicine.

show abstract

Section: Spheroids and Organoids For Personalized Medicinementioning

confidence: 99%

Promising Applications of Tumor Spheroids and Organoids for Personalized Medicine

Gilazieva

Ponomarev

Rutland

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…Some other studies have also established the effectiveness of cancer organoids in drug screening. However, a majority of the studies did not correlate the results from drug screening with clinical response [24,28,29], because surgically resected cancer tissues were used as original specimens of the cancer organoids. It is known that the postoperative recurrence of the tumor and the prognosis of patients does not depend solely on the response of the tumor to chemotherapeutic drugs, but is also attributed to the negative margin, lymph node metastases, and the extent of vascular invasion.…”

Section: Discussionmentioning

confidence: 99%

Conversion Therapy of Intrahepatic Cholangiocarcinoma Is Associated with Improved Prognosis and Verified by a Case of Patient-Derived Organoid

Wang

Yun

Guo

et al. 2021

Cancers

View full text Add to dashboard Cite

This study was performed to determine the efficacy of conversion therapy in intrahepatic cholangiocarcinoma (IHCC) and explore the feasibility of cancer organoid to direct the conversion therapy of IHCC. Patient data were retrospectively reviewed in this study and cancer organoids were established using tissues obtained from two patients. A total of 42 patients with IHCC received conversion therapy, 9 of whom were downstaged successfully, and another 157 patients were initially resectable. Kaplan–Meier curves showed that the successfully downstaged patients had a significantly improved overall survival compared to those in whom downstaging was unsuccessful (p = 0.017), and had a similar overall survival to that of initially resectable patients (p = 0.965). The IHCC organoid was successfully established from one of two obtained tissues. Routine hematoxylin and eosin staining and immunohistological staining found the organoid retained the histopathological characteristics of the original tissues. Whole exome sequencing results indicated the IHCC organoid retained appropriately 87% of the variants in the original tissue. Gemcitabine and paclitaxel exhibited the strongest inhibitory effects on the cancer organoid as determined using drug screening tests, consistent with the levels of efficacy observed in the patient from whom it was derived. This study indicates that conversion therapy could improve the survival of patients with IHCC despite its low success rate, and it may be directed by cancer organoids though this is merely a proof of feasibility.

show abstract

“…While the in vivo studies are a critical validation step in the pipeline, these studies are costly and time consuming. Future iterations of the pipeline that exploit continued improvement in patient-derived models, such as patient-derived organoids [16,35,36], are sure to improve the speed and cost-effectiveness of the pipeline and will further enable rapid translation of lead candidates into clinical practice [37]. Fifth, and perhaps most critically, the ability to test these candidates in veterinary clinical trials "closes the loop" of drug .…”

Section: Discussionmentioning

confidence: 99%

A cross-species drug discovery pipeline to identify and validate new treatments for osteosarcoma

Somarelli

Rupprecht

Altunel

et al. 2020

Preprint

View full text Add to dashboard Cite

Purpose: Osteosarcoma is a rare but aggressive bone cancer that occurs primarily in children. Like other rare cancers, treatment advances for osteosarcoma have stagnated, with little improvement in survival for the past several decades. Developing new treatments has been hampered by extensive genomic heterogeneity and limited access to patient samples to study the biology of this complex disease. Experimental design: To overcome these barriers, we combined the power of comparative oncology with patient-derived models of cancer and high-throughput chemical screens in a cross-species drug discovery pipeline. Results: Coupling in vitro high-throughput drug screens on low-passage and established cell lines with in vivo validation in patient-derived xenografts we identify the proteasome and CRM1 nuclear export pathways as therapeutic sensitivities in osteosarcoma, with dual inhibition of these pathways inducing synergistic cytotoxicity. Conclusions: These collective efforts provide an experimental framework and set of new tools for osteosarcoma and other rare cancers to identify and study new therapeutic vulnerabilities.

show abstract

Patient-Derived Organoids from Multiple Colorectal Cancer Liver Metastases Reveal Moderate Intra-patient Pharmacotranscriptomic Heterogeneity

Cited by 77 publications

References 56 publications

Promising Applications of Tumor Spheroids and Organoids for Personalized Medicine

Promising Applications of Tumor Spheroids and Organoids for Personalized Medicine

Conversion Therapy of Intrahepatic Cholangiocarcinoma Is Associated with Improved Prognosis and Verified by a Case of Patient-Derived Organoid

A cross-species drug discovery pipeline to identify and validate new treatments for osteosarcoma

Contact Info

Product

Resources

About