ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2016
The anti-ovarian cancer activity by WYE-132, a mTORC1/2 dual inhibitor.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Targeting protein synthesis pathways in MYC-amplified medulloblastoma.Discover oncology · 2025Review
- The mitochondrial protein YME1 Like 1 is important for non-small cell lung cancer cell growth.International journal of biological sciences · 2023Article
- GNE-493 inhibits prostate cancer cell growth via Akt-mTOR-dependent and -independent mechanisms.Cell death discovery · 2022Article
- Identification of Gαi3 as a novel molecular therapeutic target of cervical cancer.International journal of biological sciences · 2022Article
- Identification of Gαi3 as a promising target for osteosarcoma treatment.International journal of biological sciences · 2022Article
- The Anti-Non-Small Cell Lung Cancer Cell Activity by a mTOR Kinase Inhibitor PQR620.Frontiers in oncology · 2021Article
- Evaluation of Hsp90 and mTOR inhibitors as potential drugs for the treatment of TSC1/TSC2 deficient cancer.PloS one · 2021Article
- BRDT promotes ovarian cancer cell growth.Cell death & disease · 2020Article
- Article
- GDC-0349 inhibits non-small cell lung cancer cell growth.Cell death & disease · 2020Article
- Article
- Kinase Inhibitors and Ovarian Cancer.Cancers · 2019Review
- microRNA-200a downregulation in human glioma leads to Gαi1 over-expression, Akt activation, and cell proliferation.Oncogene · 2018Article
- PI3K/AKT/mTOR Pathway in Ovarian Cancer Treatment: Are We on the Right Track?Geburtshilfe und Frauenheilkunde · 2017Article
- Preclinical study of CC223 as a potential anti-ovarian cancer agent.Oncotarget · 2017Article
- Everolimus (RAD001) sensitizes prostate cancer cells to docetaxel by down-regulation of HIF-1α and sphingosine kinase 1.Oncotarget · 2016Article
- New Insights into mTOR Signal Pathways in Ovarian-Related Diseases: Polycystic Ovary Syndrome and Ovarian CancerAsian Pacific journal of cancer prevention : APJCP · 2016Article
- Vascular endothelial growth factor A as predictive marker for mTOR inhibition in relapsing high-grade serous ovarian cancer.BMC systems biology · 2016Article
- Sphingosine-1 Phosphate: A New Modulator of Immune Plasticity in the Tumor Microenvironment.Frontiers in oncology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial ovarian cancer is the most common and lethal gynecological cancer in USA and around the world, causing major mortality annually. In the current study, we investigated the potential anti-ovarian cancer activity of WYE-132, a mammalian target of rapamycin (mTOR) complex 1/2 (mTORC1/2) dual inhibitor. Our results showed that WYE-132 potently inhibited proliferation of primary and established human ovarian cancer cells. Meanwhile, WYE-132 induced caspase-dependent apoptosis in ovarian cancer cells. At the molecular level, WYE-132 blocked mTORC1/2 activation and inhibited expression of mTOR-regulated genes (cyclin D1 and hypoxia-inducible factor 1α). Interestingly, introducing a constitutively active AKT (caAKT), which restored mTORC1/2 activation in WYE-132-treated ovarian cancer cells, only mitigated (but not abolished) WYE-132-mediated growth inhibition and apoptosis. Further studies showed that WYE-132 inhibited sphingosine kinase-1 (SphK1) activity, leading to pro-apoptotic ceramide production in ovarian cancer cells. Meanwhile, WYE-132-induced cytotoxicity against ovarian cancer cells was inhibited by sphingosine-1-phosphate (S1P) but was aggravated by SphK1 inhibitor SKI-II or C6 ceramide. In vivo, WYE-132 inhibited ovarian cancer cell growth, and its activity was further enhanced when co-administrated with paclitaxel (Taxol). These results demonstrate that WYE-132 inhibits ovarian cancer cell proliferation through mTOR-dependent and mTOR-independent mechanisms and indicate a potential value of WYE-132 in ovarian cancer treatment.
Indexed as
Identifiers
What OpenQuestion holds
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.