ArticleCancer research2022
Epithelial-to-Mesenchymal Transition Supports Ovarian Carcinosarcoma Tumorigenesis and Confers Sensitivity to Microtubule Targeting with Eribulin.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Epithelial-mesenchymal transition in carcinoma: navigating phenotypic states to target resistance and metastasis.Cancer metastasis reviews · 2026Review
- An Aggressive Neoplasm with Mixed Epithelial and Sarcoma-like Features, of Uncertain Primary Origin, Presenting as an Upper Lip Mass: A Case Report.Journal of clinical medicine · 2026Article
- Ovarian cancer.Nature reviews. Disease primers · 2026Review
- Effects of Eribulin on Epithelial-Mesenchymal Plasticity in Patient-Derived Breast Cancer Cultures and Excised Tissues.Cancers · 2026Article
- High-throughput drug screening identifies EGFR/MAPK pathway targeting sensitivities in organoid models of ovarian carcinosarcoma.Journal of experimental & clinical cancer research : CR · 2026Article
- EMT and cancer: what clinicians should know.Nature reviews. Clinical oncology · 2025Review
- From Defense to Disease: How the Immune System Fuels Epithelial-Mesenchymal Transition in Ovarian Cancer.International journal of molecular sciences · 2025Review
- Farletuzumab ecteribulin and MORAb-109, folate receptor alpha and mesothelin targeting antibody-drug conjugates, show activity in poor prognosis gynaecological cancer models.Clinical and translational medicine · 2025Article
- Case Report: Genomic insights into prostate adenocarcinoma transdifferentiation to carcinosarcoma due to lineage plasticity.Frontiers in oncology · 2025Article
- Genomics of ovarian cancers and the potential of precision medicine.Therapeutic advances in medical oncology · 2025Review
- Molecular characteristics of tubo-ovarian carcinosarcoma at different anatomic locations.Virchows Archiv : an international journal of pathology · 2024Article
- Teratoma combined with struma ovarii and sarcomatoid carcinoma: a case report and review of the literature.BMC women's health · 2024Review
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- Compartment-specific multiomic profiling identifies SRC and GNAS as candidate drivers of epithelial-to-mesenchymal transition in ovarian carcinosarcoma.British journal of cancer · 2024Article
- Ovarian carcinosarcoma is highly aggressive compared to other ovarian cancer histotypes.Frontiers in oncology · 2024Article
- IGJ suppresses breast cancer growth and metastasis by inhibiting EMT via the NF‑κB signaling pathway.International journal of oncology · 2023Article
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- The microtubule inhibitor eribulin demonstrates efficacy in platinum-resistant and refractory high-grade serous ovarian cancer patient-derived xenograft models.Therapeutic advances in medical oncology · 2023Article
Corrections and comments
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Authors and funding
35 authors at 8 institutions in 3 countries.
Funding
Abstract
Ovarian carcinosarcoma (OCS) is an aggressive and rare tumor type with limited treatment options. OCS is hypothesized to develop via the combination theory, with a single progenitor resulting in carcinomatous and sarcomatous components, or alternatively via the conversion theory, with the sarcomatous component developing from the carcinomatous component through epithelial-to-mesenchymal transition (EMT). In this study, we analyzed DNA variants from isolated carcinoma and sarcoma components to show that OCS from 18 women is monoclonal. RNA sequencing indicated that the carcinoma components were more mesenchymal when compared with pure epithelial ovarian carcinomas, supporting the conversion theory and suggesting that EMT is important in the formation of these tumors. Preclinical OCS models were used to test the efficacy of microtubule-targeting drugs, including eribulin, which has previously been shown to reverse EMT characteristics in breast cancers and induce differentiation in sarcomas. Vinorelbine and eribulin more effectively inhibited OCS growth than standard-of-care platinum-based chemotherapy, and treatment with eribulin reduced mesenchymal characteristics and N-MYC expression in OCS patient-derived xenografts. Eribulin treatment resulted in an accumulation of intracellular cholesterol in OCS cells, which triggered a downregulation of the mevalonate pathway and prevented further cholesterol biosynthesis. Finally, eribulin increased expression of genes related to immune activation and increased the intratumoral accumulation of CD8+ T cells, supporting exploration of immunotherapy combinations in the clinic. Together, these data indicate that EMT plays a key role in OCS tumorigenesis and support the conversion theory for OCS histogenesis. Targeting EMT using eribulin could help improve OCS patient outcomes. SIGNIFICANCE: Genomic analyses and preclinical models of ovarian carcinosarcoma support the conversion theory for disease development and indicate that microtubule inhibitors could be used to suppress EMT and stimulate antitumor immunity.
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