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Organoids and epithelial ovarian cancer - a future tool for personalized treatment decisions? (Review).

ABSTRACT: Epithelial ovarian cancer (EOC) is the 5th leading cause of cancer-associated death in females worldwide. Although 80% of cases respond well to initial treatment, >70% develop recurrent disease and become chemoresistant within the first two years. Therefore, there is a great need for predictive biomarkers to guide treatment. In the era of precision medicine, organoids are studied as a functional method to predict treatment response to oncological treatment. The overall purpose of the present systematic review was to uncover the current status of patient-derived organoids and their ability to perform drug screenings for EOC. A systematic search for studies investigating ovarian cancer and organoids was performed using PubMed and the Cochrane Library. A total of 10 studies fulfilled the inclusion criteria. The growth rates of organoids were described in six studies and varied between 29 and 90%. Only four studies included data on clinical outcomes and indicated a positive correlation between clinical response and drug screening results. Inter- and intratumoral heterogeneity was examined in seven studies. They all suggested that the organoids recapture the tumor heterogeneity. Only one study performed drug screenings on organoids obtained from different tumor sites and metastasis from the same patient with EOC and revealed a different response to at least one drug for all patients. In conclusion, organoids may provide a platform for predicting the clinical response to chemotherapy and gene-targeting therapy. However, the results are only exploratory and the number of published drug screening studies is minimal. Further research is required to prove that organoids are able to support the choice of oncological treatment in patients with EOC.

SUBMITTER: Sisman Y

PROVIDER: S-EPMC8719262 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:High-grade serous ovarian carcinoma (HGSOC) is the most common type of epithelial ovarian cancer. The majority of cases are diagnosed at advanced stages, when intraperitoneal (IP) spread has already occurred. Despite significant surgical and chemotherapeutic advances in HGSOC treatment over the past decades, survival rates with HGSOC have only modestly improved. Chimeric antigen receptor (CAR)-T cells enable T cells to directly bind to tumor-associated antigens in a major histocompatibility complex-independent manner, thereby inducing tumor rejection. While CAR-T cell therapy shows great promise in hematological malignancies, its use in solid tumors is limited. Therefore, innovative approaches are needed to increase the specificity of CAR-modified T cells against solid tumors. The aim of this study was to assess the efficacy and safety of intraperitoneal (IP) versus intravenous (IV) CAR-T cell therapy in the treatment of HGSOC. We constructed a CAR that targets the ErbB2/HER2 protein (ErbB2CAR), which is overexpressed in HGSOC, and evaluated the functionality of ErbB2CAR on ovarian cancer cell lines (OVCAR8, SKOV3, and NAR). Our findings show that an IP injection of ErbB2CAR-T cells to tumor-bearing mice led to disease remission and increased survival compared to the IV route. Moreover, we found that IP-injected ErbB2CART cells circulate to a lesser extent, making them safer for non-tumor tissues than IV-injected cells. Further supporting our findings, we show that the effect of ErbB2CAR-T cells on primary HGSOC tumors is correlated with ErbB2 expression. Together, these data demonstrate the advantages of an IP administration of CAR-T cells over IV administration, offering not only a safer strategy but also the potential for counteracting the effect of ErbB2CAR in HGSOC. Significance: IP-injected ErbB2CAR-T cells led to disease remission and increased survival compared to the IV route. These findings demonstrate the advantages of IP administration, offering a safe treatment strategy with the potential for counteracting the effect of ErbB2CAR in HGSOC.

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Organoids and epithelial ovarian cancer - a future tool for personalized treatment decisions? (Review).

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