Current status and perspectives of patient-derived rare cancer models

Kondo, Tadashi

doi:10.1007/s13577-020-00391-1

Cited by 18 publications

(7 citation statements)

References 122 publications

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“…232 regimens involving 63 drugs were tested, and 17 treatment plans suggested by PDTX modeling were engaged on the patients in 11 cases with 15 plans achieved long-term PR. Subsequently, multiple studies [31][32][33][34][35] reported PDTX guided personalized medication that cover both chemotherapy and targeted therapy illustrating the advantage of PDTX for therapy optimization. In this study, 3 patients (130111, 110150 and 110160) also continued the medication following the guidance of PDTX and obtained SD.…”

Section: Discussionmentioning

confidence: 99%

A multicenter clinical study: personalized medication for advanced gastrointestinal carcinomas with the guidance of patient-derived tumor xenograft (PDTX)

Cheng

Qin

Jin

et al. 2021

J Cancer Res Clin Oncol

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Background: Establish patient-derived tumor xenograft (PDTX) from advanced GICs and assess the clinical value and applicability of PDTX for the treatment of advanced GICs. Method:Patients with advanced GICs were enrolled in a registered multi-center clinical study (ChiCTR-OOC-17012731). The performance of PDTX were evaluated includes: analyzing factors that affect the engraftment rate, comparing the histological consistency between primary tumors and tumorgrafts, examining the concordance between the drug effectiveness in PDTXs and clinical responses, and Identifying genetic variants and other factors associated with prognosis.Results: Thirty-three patients were enrolled in the study with the engraftment rate of 75.8% (25/33). The successfulness of engraftment was independent of age, cancer types, pathological stages of tumors, and particularly sampling methods. Tumorgrafts kept same histopathological characteristics as primary tumors. Forty-nine regimens involving twenty-eight drugs were tested in seventeen tumorgrafts. The median time for drug testing was 134.5 day. The follow up information of 10 regimens from 9 patients were obtained. / 22The concordance of drug effectiveness in PDTXs and clinical responses was 100%. The tumor mutation burden (TMB) was correlated with the effectiveness of single drug regimens, while the outgrowth time of tumorgrafts was associated with the effectiveness of combined regimens. Conclusion:The engraftment rate in advanced GICs is higher than other cancers and meets the general acceptable standard of applying personalized therapeutic strategies. Tumorgrafts from PDTX kept attributes of primary tumor. Predictions from PDTX modeling highly agree with the clinical drug responses. PDTX may already be clinical applicable for the personalized medication in advanced GICs.

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Section: Discussionmentioning

confidence: 99%

A multicenter clinical study: personalized medication for advanced gastrointestinal carcinomas with the guidance of patient-derived tumor xenograft (PDTX)

Cheng

Qin

Jin

et al. 2021

J Cancer Res Clin Oncol

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“…Functional precision medicine -based on testing drug responses on patient tumours to identify treatment regimens -has been proposed as a more direct alternative, as it does not require any a priori knowledge of the tumour molecular profile or other characteristics 160,168 . Organoids are ideally suited for functional precision medicine because they are straightforward to establish, have high similarity with the tissue of origin, are tractable 157,169 and have been deployed to identify therapeutic leads in numerous tumours 170 , including rare cancers that tend to be understudied and poorly characterized at the molecular level 15,150,171,172 . Recently, organoids established from patient-derived xenografts were used to identify eribulin as therapy for a patient with recurrent triple-negative breast cancer 173 .…”

Section: Precision Medicine Applicationsmentioning

confidence: 99%

Organoids

Zhao

Chen

Dowbaj

et al. 2022

Nat Rev Methods Primers

286

152

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Organoids are simple tissue-engineered cell-based in vitro models that recapitulate many aspects of the complex structure and function of the corresponding in vivo tissue. They can be dissected and interrogated for fundamental mechanistic studies on development, regeneration and repair in human tissues, and can also be used in diagnostics, disease modelling, drug discovery and personalized medicine. Organoids are derived from either pluripotent or tissue-resident stem (embryonic or adult) or progenitor or differentiated cells from healthy or diseased tissues, such as tumours. To date, numerous organoid engineering strategies that support organoid culture and growth, proliferation, differentiation and maturation have been reported. This Primer highlights the rationale underlying the selection and development of these materials and methods to control the cellular/tissue niche; and therefore, the structure and function of the engineered organoid. We also discuss key considerations for generating robust organoids, such as those related to cell isolation and seeding, matrix and soluble factor selection, physical cues and integration. The general standards for data quality, reproducibility and deposition within the organoid community are also outlined. Lastly, we conclude by elaborating on the limitations of organoids in different applications, and the key priorities in organoid engineering for the coming years. Experimentation Cell sourceUnder defined physicochemical conditions, tissues such as small intestine 7 , colon 29,30 , stomach 31,32 , oesophagus 29 , tongue 33 , liver [34][35][36][37] , lung 14 , pancreas [38][39][40] , heart 41 , ear 42 and skin 43 have been obtained from iPSCs, adult or fetal cells and either stem/progenitor cells or differentiated cells. The starting cellular population for any given organoid is of prime importance, affecting not only the variability and heterogeneity in the structures obtained but also the function of the tissue they aim to model. To establish tissue-derived organoids or cancer organoids, tissue-resident stem/progenitor/differentiated cells or tumour cells, respectively, are obtained through an optimized tissue dissociation method. For iPSC-derived organoids, iPSC lines are established and fully characterized as the starting cells. Patient/tissue-derived stem cells are obtained through an optimized tissue dissociation method and then embedded into a 3D matrix mimicking stem cell niches. iPSCs can be maintained and expanded as undifferentiated clonal populations on feeder cells. To exemplify the generation of tissue-derived organoids we use intestinal organoids as an example (Fig. 2a), as this was the first tissue-derived organoid type established 7 . The small intestine and colon are opened longitudinally, washed and then cut into 2-4 mm fragments to increase the surface area for enzymatic digestion or further mechanical dissociation. EDTA treatment is used to chelate calcium, disrupting cell-cell adhesion and tissue integrity 44 . Larger tissue fragments and whole cells ...

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“…Several literature reviews have been recently published on three-dimensional sarcoma models [ 45 , 46 , 47 ]. These publications mostly report on sarcoma-derived three-dimensional cultures or spheroids and only underline the importance of the generation of advanced sarcoma organoids.…”

Section: Discussionmentioning

confidence: 99%

Organoids: A New Chapter in Sarcoma Diagnosis and Treatment

Psilopatis

Kokkali

Palamaris

et al. 2022

IJMS

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Sarcomas are malignant tumors of mesenchymal origin that can occur at any age. The rarity of these tumors in combination with the vast number of histological subtypes render the study of sarcomas challenging. Organoids represent complex three-dimensional cell culture systems, deriving from stem cells and preserving the capacity to differentiate into the cell types of their tissue of origin. The aim of the present review is to study the current status of patient-derived organoids, as well as their potential to model tumorigenesis and perform drug screenings for sarcomas. In order to identify relevant studies, a literature review was conducted and we were able to identify 16 studies published between 2019 and 2022. The current manuscript represents the first comprehensive review of the literature focusing on the use of organoids for disease modelling and drug sensitivity testing in diverse sarcoma subtypes.

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Current status and perspectives of patient-derived rare cancer models

Cited by 18 publications

References 122 publications

A multicenter clinical study: personalized medication for advanced gastrointestinal carcinomas with the guidance of patient-derived tumor xenograft (PDTX)

A multicenter clinical study: personalized medication for advanced gastrointestinal carcinomas with the guidance of patient-derived tumor xenograft (PDTX)

Organoids

Organoids: A New Chapter in Sarcoma Diagnosis and Treatment

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