Ex vivo chemosensitivity assay using primary ovarian cancer organoids for predicting clinical response and screening effective drugs

Ito, Yu; Kondo, Jumpei; Masuda, Masao; Matsuzaki, Shinya; Onuma, Kunishige; Kanda, Mizuki; Watanabe, Yuko; Sakaguchi, Hitomi; Yoshino, Kiyoshi; Ueda, Yutaka; Kamiura, Shoji; Kimura, Tadashi; Inoue, Masahiro

doi:10.1007/s13577-022-00827-w

Cited by 5 publications

(6 citation statements)

References 40 publications

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“…Ito et al performed sensitivity testing on paclitaxel and carboplatin using organoids prepared from cancer tissue primary spheroids (CTOS) of OC patients undergoing chemotherapy, with a success rate of 84% ( Ito et al, 2023 ). Extensive sensitivity was observed in organoids of both drugs.…”

Section: Ovarian Cancer Organoidsmentioning

confidence: 99%

Research progress on the application of organoids in gynecological tumors

Shen,

Wang,

Wang

et al. 2024

Front. Pharmacol.

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Organoids are in vitro 3D models that maintain their own tissue structure and function. They largely overcome the limitations of traditional tumor models and have become a powerful research tool in the field of oncology in recent years. Gynecological malignancies are major diseases that seriously threaten the life and health of women and urgently require the establishment of models with a high degree of similarity to human tumors for clinical studies to formulate individualized treatments. Currently, organoids are widely studied in exploring the mechanisms of gynecological tumor development as a means of drug screening and individualized medicine. Ovarian, endometrial, and cervical cancers as common gynecological malignancies have high morbidity and mortality rates among other gynecological tumors. Therefore, this study reviews the application of modelling, drug efficacy assessment, and drug response prediction for ovarian, endometrial, and cervical cancers, thereby clarifying the mechanisms of tumorigenesis and development, and providing precise treatment options for gynecological oncology patients.

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Section: Ovarian Cancer Organoidsmentioning

confidence: 99%

Research progress on the application of organoids in gynecological tumors

Shen,

Wang,

Wang

et al. 2024

Front. Pharmacol.

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“…8,49,52 The overall success rate of PDOs in EOC was 55%-100%. 12,54,64,68 And this depends on various factors including the use of growth factors and ECM. 4.1.1 | Media and growth factors Some low-grade tumors like LGSC and borderline ovarian tumor (BOT) can be cultured in media with altered composition from those used to culture normal tissues.…”

Section: Generation Of Pdos In Eocmentioning

confidence: 99%

“…Short‐term and long‐term cultures have been reported, and EOC organoids can be expanded up to 30 passages or more than 1 year 8,49,52 . The overall success rate of PDOs in EOC was 55%–100% 12,54,64,68 . And this depends on various factors including the use of growth factors and ECM.…”

Section: Patient‐derived Organoids In Epithelial Ovarian Cancermentioning

confidence: 99%

“…It is less tedious and less expensive compared to PDXs. PDOs have been utilized for drug screening in EOC, such as carboplatin, paclitaxel, gemcitabine, topotecan, poly (ADP‐ribose) polymerase inhibitor, and immunotherapy 9,49,55,56,68,103 . However, these were limited to small case series without proper sample size calculation.…”

Section: Applicationsmentioning

confidence: 99%

“…PDOs have been utilized for drug screening in EOC, such as carboplatin, paclitaxel, gemcitabine, topotecan, poly (ADP-ribose) polymerase inhibitor, and immunotherapy. 9,49,55,56,68,103 However, these were limited to small case series without proper sample size calculation. Several clinical trials are ongoing to evaluate the efficacy of PDOs in predicting drug response and survival in EOC (NCT04555473, NCT05290961, NCT05175326, NCT04768270, and NCT05537844).…”

Section: Personalized Medicine: Drug Screening and New Drug Developmentmentioning

confidence: 99%

See 2 more Smart Citations

Patient‐derived organoid culture in epithelial ovarian cancers—Techniques, applications, and future perspectives

Chan,

Mo,

et al. 2023

Cancer Medicine

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Epithelial ovarian cancer (EOC) is a heterogeneous disease composed of different cell types with different molecular aberrations. Traditional cell lines and mice models cannot recapitulate the human tumor biology and tumor microenvironment (TME). Patient‐derived organoids (PDOs) are freshly derived from patients' tissues and are then cultured with extracellular matrix and conditioned medium. The high concordance of epigenetic, genomic, and proteomic landscapes between the parental tumors and PDOs suggests that PDOs can provide more reliable results in studying cancer biology, allowing high throughput drug screening, and identifying their associated signaling pathways and resistance mechanisms. However, despite having a heterogeneity of cells in PDOs, some cells in TME will be lost during the culture process. Next‐generation organoids have been developed to circumvent some of the limitations. Genetically engineered organoids involving targeted gene editing can facilitate the understanding of tumorigenesis and drug response. Co‐culture systems where PDOs are cultured with different cell components like immune cells can allow research using immunotherapy which is otherwise impossible in conventional cell lines. In this review, the limitations of the traditional in vitro and in vivo assays, the use of PDOs, the challenges including some tips and tricks of PDO generation in EOC, and the future perspectives, will be discussed.

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Exploiting a living biobank to delineate mechanisms underlying disease-specific chromosome instability

Nelson,

Barnes,

Tighe

et al. 2023

Chromosome Res

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Chromosome instability (CIN) is a cancer hallmark that drives tumour heterogeneity, phenotypic adaptation, drug resistance and poor prognosis. High-grade serous ovarian cancer (HGSOC), one of the most chromosomally unstable tumour types, has a 5-year survival rate of only ~30% — largely due to late diagnosis and rapid development of drug resistance, e.g., via CIN-driven ABCB1 translocations. However, CIN is also a cell cycle vulnerability that can be exploited to specifically target tumour cells, illustrated by the success of PARP inhibitors to target homologous recombination deficiency (HRD). However, a lack of appropriate models with ongoing CIN has been a barrier to fully exploiting disease-specific CIN mechanisms. This barrier is now being overcome with the development of patient-derived cell cultures and organoids. In this review, we describe our progress building a Living Biobank of over 120 patient-derived ovarian cancer models (OCMs), predominantly from HGSOC. OCMs are highly purified tumour fractions with extensive proliferative potential that can be analysed at early passage. OCMs have diverse karyotypes, display intra- and inter-patient heterogeneity and mitotic abnormality rates far higher than established cell lines. OCMs encompass a broad-spectrum of HGSOC hallmarks, including a range of p53 alterations and BRCA1/2 mutations, and display drug resistance mechanisms seen in the clinic, e.g., ABCB1 translocations and BRCA2 reversion. OCMs are amenable to functional analysis, drug-sensitivity profiling, and multi-omics, including single-cell next-generation sequencing, and thus represent a platform for delineating HGSOC-specific CIN mechanisms. In turn, our vision is that this understanding will inform the design of new therapeutic strategies.

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Ex vivo chemosensitivity assay using primary ovarian cancer organoids for predicting clinical response and screening effective drugs

Cited by 5 publications

References 40 publications

Research progress on the application of organoids in gynecological tumors

Research progress on the application of organoids in gynecological tumors

Patient‐derived organoid culture in epithelial ovarian cancers—Techniques, applications, and future perspectives

Exploiting a living biobank to delineate mechanisms underlying disease-specific chromosome instability

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