A platform for efficient establishment and drug-response profiling of high-grade serous ovarian cancer organoids

Senkowski, Wojciech; Gall-Mas, Laura; Falco, Matías M.; Li, Yilin; Lavikka, Kari; Kriegbaum, Mette C.; Oikkonen, Jaana; Bulanova, Daria; Pietras, Elin J.; Vähärautio, Anna; Chen, Yan-Jun; Erkan, Erdoğan Pekcan; Dai, Jun; Lundgren, Anastasia; Høg, Mia Kristine Grønning; Larsen, Ida Marie; Lamminen, Tarja; Kaipio, Katja; Huvila, Jutta; Virtanen, Anni; Engelholm, Lars H.; Christiansen, P.; Santoni-Rugiu, Eric; Huhtinen, Kaisa; Carpén, Olli; Hynninen, Johanna; Hautaniemi, Sampsa; Wennerberg, Krister

doi:10.1016/j.devcel.2023.04.012

Cited by 17 publications

(33 citation statements)

References 57 publications

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“…45 However, a recent article showed that immune cells and stromal cells were retained even in long-term PDO culture using cryopreserved tumors as detected by single-cell RNA sequencing (scRNA-seq). 60 Another method is microfluidic 3D culture or the air-liquid interface (ALI) culture, in which the native TIME is preserved without the need for subsequent reconstitution of immune or stromal cells. 14,61 In microfluidic 3D culture, organoids from digested tissues are mixed with collagen forming a spheroid that preserves the TIME components, 14,62 and are then injected into a microfluidic culture device which often contains a central gel channel flanked by two media channels on both sides.…”

Section: Source Of Cellsmentioning

confidence: 99%

“…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. 8,54,60 In high-grade tumors, the choice of media and growth factors is more complex, and the composition is not standardized and varied in different papers (Table 1). Both commercially available media and self-prepared media had been used, though there were not too many commercially available media for EOC.…”

Section: Generation Of Pdos In Eocmentioning

confidence: 99%

“…Using cryopreserved specimens in HGSC, Senkowski et al demonstrated that the condition of the media affected the growth of organoids and the response to drugs like carboplatin and paclitaxel. 60 Growth factors such as fibroblast growth factor-10 (FGF10), neuregulin1 (NRG1), nicotinamide, p38 mitogenactivated protein kinase inhibitor (SB203580), and transforming growth factor-beta (TGF-β) inhibitor (A83-01 could stimulate the organoid development. 49,53,54,69 FGF-4 promotes the tumorigenicity of cancer stem cells, and including FGF-4 in the medium could enhance organoid formation after passaging.…”

Section: Generation Of Pdos In Eocmentioning

confidence: 99%

“…49,53,54,69 FGF-4 promotes the tumorigenicity of cancer stem cells, and including FGF-4 in the medium could enhance organoid formation after passaging. 60 R-spondin, bone morphogenetic (BMP) inhibitor Noggin, and epidermal growth factor (EGF) are also required for the stem cells to undergo self-renewal and differentiation into different cell lineages, 45 though some groups reported that the use of Noggin and EGF might reduce organoid formation. 60 Short-term (2-3 weeks or within 1-2 passages) 49 and longterm (4 weeks to 3 months, or more than 6 passages) 52,60,70 cultures of mouse and human organoids were reported.…”

Section: Generation Of Pdos In Eocmentioning

confidence: 99%

“…49 Wnt pathway activation was shown to induce growth arrest in HGSC organoids, and so long-term culture of EOC organoids should be carried out in a low Wnt environment. 52,60 Several groups also showed that the addition of beta-estradiol could promote organoid formation and growth over passaging in HGSC. 8,52,53,60 4.1.2 | ECM ECM is a fibrous network of macromolecules that mainly contains laminin, collagen IV, heparan sulfate proteoglycans, and entactin/nidogen.…”

Section: Generation Of Pdos In Eocmentioning

confidence: 99%

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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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Section: Source Of Cellsmentioning

confidence: 99%

Section: Generation Of Pdos In Eocmentioning

confidence: 99%

Section: Generation Of Pdos In Eocmentioning

confidence: 99%

Section: Generation Of Pdos In Eocmentioning

confidence: 99%

Section: Generation Of Pdos In Eocmentioning

confidence: 99%

See 3 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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Establishment of patient‐derived organoids for guiding personalized therapies in breast cancer patients

Wu,

Wang,

Zhang

et al. 2024

Intl Journal of Cancer

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Breast cancer has become the most commonly diagnosed cancer. The intra‐ and interpatient heterogeneity induced a considerable variation in treatment efficacy. There is an urgent requirement for preclinical models to anticipate the effectiveness of individualized drug responses. Patient‐derived organoids (PDOs) can accurately recapitulate the architecture and biological characteristics of the origin tumor, making them a promising model that can overtake many limitations of cell lines and PDXs. However, it is still unclear whether PDOs‐based drug testing can benefit breast cancer patients, particularly those with tumor recurrence or treatment resistance. Fresh tumor samples were surgically resected for organoid culture. Primary tumor samples and PDOs were subsequently subjected to H&E staining, immunohistochemical (IHC) analysis, and whole‐exome sequencing (WES) to make comparisons. Drug sensitivity tests were performed to evaluate the feasibility of this model for predicting patient drug response in clinical practice. We established 75 patient‐derived breast cancer organoid models. The results of H&E staining, IHC, and WES revealed that PDOs inherited the histologic and genetic characteristics of their parental tumor tissues. The PDOs successfully predicted the patient's drug response, and most cases exhibited consistency between PDOs' drug susceptibility test results and the clinical response of the matched patient. We conclude that the breast cancer organoids platform can be a potential preclinical tool used for the selection of effective drugs and guided personalized therapies for patients with advanced breast cancer.

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Organoids in ovarian cancer: a platform for disease modeling, precision medicine, and drug assessment

Hu,

Sun,

Chen

et al. 2024

J Cancer Res Clin Oncol

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Ovarian cancer (OC) is a major cause of gynecological cancer mortality, necessitating enhanced research. Organoids, cellular clusters grown in 3D model, have emerged as a disruptive paradigm, transcending the limitations inherent to conventional models by faithfully recapitulating key morphological, histological, and genetic attributes. This review undertakes a comprehensive exploration of the potential in organoids derived from murine, healthy population, and patient origins, encompassing a spectrum that spans foundational principles to pioneering applications. Organoids serve as preclinical models, allowing us to predict how patients will respond to treatments and guiding the development of personalized therapies. In the context of evaluating new drugs, organoids act as versatile platforms, enabling thorough testing of innovative combinations and novel agents. Remarkably, organoids mimic the dynamic nature of OC progression, from its initial formation to the spread to other parts of the body, shedding light on intricate details that hold significant importance. By functioning at an individualized level, organoids uncover the complex mechanisms behind drug resistance, revealing strategic opportunities for effective treatments.

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A platform for efficient establishment and drug-response profiling of high-grade serous ovarian cancer organoids

Cited by 17 publications

References 57 publications

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

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

Establishment of patient‐derived organoids for guiding personalized therapies in breast cancer patients

Organoids in ovarian cancer: a platform for disease modeling, precision medicine, and drug assessment

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