Harnessing preclinical models for the interrogation of ovarian cancer

Qin, Tianyu; Fan, Junpeng; Lü, Fang; Zhang, Li; Liu, Chen; Qiyue, Xiong; Zhao, Yang; Chen, Gang; Sun, Chaoyang

doi:10.1186/s13046-022-02486-z

Cited by 11 publications

(13 citation statements)

References 183 publications

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“…However, CDX cannot accurately express the tumor heterogeneity and drug response among patients due to cell line limitations. Less than 10% of drug candidates are approved despite successful trials in animal models, which is only 5% for tumor drugs 10 …”

Section: Advantages and Limitations Of The Existing Preclinical Modelsmentioning

confidence: 99%

Recent advances in patient‐derived tumor organoids for reconstructing TME of head and neck cancer

Chen,

et al. 2024

J Oral Pathology Medicine

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BackgroundThe differences between existing preclinical models and the tumor microenvironment in vivo are one of the significant challenges hindering cancer therapy development. Patient‐derived tumor organoids (PDTO) can highly retain tumor heterogeneity. Thus, it provides a more reliable platform for research in tumor biology, new drug screening, and precision medicine.MethodsWe conducted a systematic review to summarise the characteristics of the existing preclinical models, the advantages of patient‐derived tumor organoids in reconstructing the tumor microenvironment, and the latest research progress. Moreover, this study deciphers organoid culture technology in the clinical precision treatment of head and neck cancer to achieve better transformation. Studies were identified through a comprehensive search of Ovid MEDLINE (Wolters Kluwer), PubMed (National Library of Medicine), web of Science (Thomson Reuters) and, Scopus (Elsevier) databases, without publication date or language restrictions.ResultsIn tumor development, the interaction between cellular and non‐cellular components in the tumor microenvironment (TME) has a crucial role. Co‐culture, Air‐liquid interface culture, microfluidics, and decellularized matrix have depicted great potential in reconstructing the tumor microenvironment and simulating tumor genesis, development, and metastasis.ConclusionAn accurate determination of stromal cells, immune cells, and extracellular matrix can be achieved by reconstructing the head and neck cancer tumor microenvironment using the PDTO model. Moreover, the interaction between head and neck cancer cells can also play an essential role in implementing the individualized precision treatment of head and neck cancer.

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Section: Advantages and Limitations Of The Existing Preclinical Modelsmentioning

confidence: 99%

Recent advances in patient‐derived tumor organoids for reconstructing TME of head and neck cancer

Chen,

et al. 2024

J Oral Pathology Medicine

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“…It is frequently identified at an advanced stage which has a dismal five-year survival rate [ 3 ]. Additionally, OC has a variety of etiological, histopathological, and biological features, characterized by slow-progressing and aggressive tumor growth [ 4 , 5 ]. In the advanced stages of OC, cancer cells spread from the ovaries to the pelvis, abdomen, lungs, or multiple secondary sites, which severely limits the efficacy of treatment options that cause fatal clinical outcomes [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Knockdown of CENPM activates cGAS-STING pathway to inhibit ovarian cancer by promoting pyroptosis

Xie,

Zhang,

Shen

et al. 2024

BMC Cancer

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Objective We aimed to screen novel gene signatures for ovarian cancer (OC) and explore the role of biomarkers in OC via regulating pyroptosis using bioinformatics analysis. Methods Differentially expressed genes (DEGs) of OC were screened from GSE12470 and GSE16709 datasets. Hub genes were determined from protein–protein interaction networks after bioinformatics analysis. The role of Centromeric protein M (CENPM) in OC was assessed by subcutaneous tumor experiment using hematoxylin–eosin and immunohistochemical staining. Tumor metastasis was evaluated by detecting epithelial-mesenchymal transition-related proteins. The proliferation, migration, and invasion were determined using cell counting kit and transwell assay. Enzyme-linked immunosorbent assay was applied to measure inflammatory factors. The mRNA and protein expression were detected using real-time quantitative PCR and western blot. Results We determined 9 hub genes (KIFC1, PCLAF, CDCA5, KNTC1, MCM3, OIP5, CENPM, KIF15, and ASF1B) with high prediction value for OC. In SKOV3 and A2780 cells, the expression levels of hub genes were significantly up-regulated, compared with normal ovarian cells. CENPM was selected as a key gene. Knockdown of CENPM suppressed proliferation, migration, and invasion of OC cells. Subcutaneous tumor experiment revealed that CENPM knockdown significantly suppressed tumor growth and metastasis. Additionally, pyroptosis was promoted in OC cells and xenograft tumors after CENPM knockdown. Furthermore, CENPM knockdown activated cGAS-STING pathway and the pathway inhibitor reversed the inhibitory effect of CENPM knockdown on viability, migration, and invasion of OC cells. Conclusion CENPM was a novel biomarker of OC, and knockdown of CENPM inhibited OC progression by promoting pyroptosis and activating cGAS-STING pathway.

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“…However, previously evaluated CSRAs have suffered from long assay times (weeks to months), poor technical performance leading to assay failure for a large proportion of the patients, and insufficient validation 12 , 13 . For patients with EOC, the establishment of a CSRA to evaluate functional treatment outcomes has only been achieved for 10–20% of the patients 14 . Therefore, validated and faster functional assays with better technical performance are needed to support effective treatment planning for EOC patients.…”

Section: Introductionmentioning

confidence: 99%

Zebrafish tumour xenograft models: a prognostic approach to epithelial ovarian cancer

Lindahl,

Fjellander,

Selvaraj

et al. 2024

npj Precis. Onc.

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Epithelial ovarian cancer (EOC) is the gynaecological malignancy with highest mortality. Although adjuvant treatment with carboplatin and paclitaxel leads to an objective response in ~80% of these patients, a majority will relapse within two years. Better methods for assessing long-term treatment outcomes are needed. To address this, we established safe and efficacious doses of carboplatin and paclitaxel using IGROV-1 zebrafish-CDX models. Then fluorescently-labelled cell suspensions from 83 tumour biopsies collected at exploratory laparotomy of women with suspected EOC were generated and 37 (45%) were successfully implanted in zebrafish larvae. Among these 19 of 27 pathology-confirmed EOC samples (70%) engrafted. These zebrafish patient-derived tumour xenograft (ZTX) models were treated with carboplatin or paclitaxel and tumour growth/regression and metastatic dissemination were recorded. In a subgroup of nine patients, four ZTX models regressed during carboplatin treatment. All four corresponding patients had >24 months PFS. Furthermore, both ZTX models established from two patients having <24 months PFS failed to regress during carboplatin treatment. Seven of eight models seeding <6 metastatic cells were established from patients having >24 months PFS. In eleven of fourteen patients, FIGO stage I + II or III tumours gave rise to ZTX models seeding <4 or >4 metastatic cells, respectively. In conclusion, ZTX models predicted patients having >24 or <24 months PFS, based on response/no response to carboplatin. Furthermore, high metastatic dissemination in ZTX models correlated to shorter PFS and more advanced disease at diagnosis. These preliminary results suggest that ZTX models could become a useful prognostic tool in EOC treatment planning.

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Harnessing preclinical models for the interrogation of ovarian cancer

Cited by 11 publications

References 183 publications

Recent advances in patient‐derived tumor organoids for reconstructing TME of head and neck cancer

Recent advances in patient‐derived tumor organoids for reconstructing TME of head and neck cancer

Knockdown of CENPM activates cGAS-STING pathway to inhibit ovarian cancer by promoting pyroptosis

Zebrafish tumour xenograft models: a prognostic approach to epithelial ovarian cancer

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