ArticleOncotarget2018
mTORC1/2 inhibition re-sensitizes platinum-resistant ovarian cancer by disrupting selective translation of DNA damage and survival mRNAs.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 50 citations in OpenAlex.
- Comparative Effects of Pairwise Combinations of Carboplatin, Everolimus, and Astaxanthin on Cell Viability, Migration, and Inflammatory Biomarkers in SKOV3 Ovarian Cancer Cells.International journal of molecular sciences · 2026Article
- Functional profiling of ovarian cancer models reveals Bcl-xL/NOTCH targeting to overcome resistance.NPJ precision oncology · 2026Article
- Phosphoproteomics Reveals L1CAM-Associated Signaling Networks in High-Grade Serous Ovarian Carcinoma: Implications for Radioresistance and Tumorigenesis.International journal of molecular sciences · 2025Article
- Ipatasertib, an oral AKT inhibitor, in combination with carboplatin exhibits anti-proliferative effects in uterine serous carcinoma.Annals of medicine · 2023Article
- Article
- Review
- Phase I study of sapanisertib with carboplatin and paclitaxel in mTOR pathway altered solid malignancies.NPJ precision oncology · 2023Review
- OSW-1 induces apoptosis and cyto-protective autophagy, and synergizes with chemotherapy on triple negative breast cancer metastasis.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Microarray analysis of breast cancer gene expression profiling in response to 2-deoxyglucose, metformin, and glucose starvation.Cancer cell international · 2022Article
- mTOR inhibition by TAK-228 is effective against growth, survival and angiogenesis in preclinical retinoblastoma models.Pharmacology research & perspectives · 2022Article
- Article
- The plasticity of mRNA translation during cancer progression and therapy resistance.Nature reviews. Cancer · 2021Review
- Inhibition of the mTOR pathway and reprogramming of protein synthesis by MDM4 reduce ovarian cancer metastatic properties.Cell death & disease · 2021Article
- Cancer Plasticity: The Role of mRNA Translation.Trends in cancer · 2021Review
- Targeting the PI3K/AKT/mTOR pathway in epithelial ovarian cancer, therapeutic treatment options for platinum-resistant ovarian cancer.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- Targeting mTOR and eIF4E: a feasible scenario in ovarian cancer therapy.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- Targeting the PI3K pathway and DNA damage response as a therapeutic strategy in ovarian cancer.Cancer treatment reviews · 2020Review
- Targeting mTOR for cancer therapy.Journal of hematology & oncology · 2019Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Platinum resistance is a major cause of treatment failure and mortality in epithelial ovarian cancer. mTORC1/2 inhibitors, which impair mRNA translation, can re-sensitize resistant ovarian cancer cells to platinum chemotherapy but the mechanism remains poorly described. Using platinum-resistant OVCAR-3 cells treated with the selective mTORC1/2 inhibitor INK128/MLN128, we conducted genome-wide transcription and translation studies and analyzed the effect on cell proliferation, AKT-mTOR signaling and cell survival, to determine whether carboplatin resistance involves selective mRNA translational reprogramming, and whether it is sensitive to mTORC1/2 inhibition. Gene ontology and Ingenuity Pathway Analysis (IPA) were used to categorize gene expression changes into experimentally authenticated biochemical and molecular networks. We show that carboplatin resistance involves increased mTORC1/2 signaling, resulting in selective translation of mRNAs involved in DNA damage and repair responses (DDR), cell cycle and anti-apoptosis (survival) pathways. Re-sensitization of ovarian cancer cell killing by carboplatin required only modest mTORC1/2 inhibition, with downregulation of protein synthesis by only 20-30%. Genome-wide transcriptomic and translatomic analyses in OVCAR-3 cells revealed that the modest downregulation of global protein synthesis by dual mTORC1/2 inhibition is associated with greater selective inhibition of DDR, cell cycle and survival mRNA translation, which was confirmed in platinum-resistant SKOV-3 cells. These data suggest a clinical path to re-sensitize platinum resistant ovarian cancer to platinum chemotherapy through partial inhibition of mTORC1/2, resulting in selective translation inhibition of DDR and anti-apoptosis protective mRNAs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.