ArticleLeukemia2012
Optimal induction of myeloma cell death requires dual blockade of phosphoinositide 3-kinase and mTOR signalling and is determined by translocation subtype.
Article in Leukemia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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
9 citing papers in PubMed, 22 citations in OpenAlex.
- Pathogenic signaling in multiple myeloma.Seminars in oncology · 2022Article
- NVP-BEZ235-induced autophagy as a potential therapeutic approach for multiple myeloma.American journal of translational research · 2019Article
- VS-5584 mediates potent anti-myeloma activity via the upregulation of a class II tumor suppressor gene, RARRES3 and the activation of Bim.Oncotarget · 2017Article
- MAF protein mediates innate resistance to proteasome inhibition therapy in multiple myeloma.Blood · 2016Article
- Review
- Signaling Pathways and Emerging Therapies in Multiple Myeloma.Current hematologic malignancy reports · 2016Review
- Novel therapeutic strategies for multiple myeloma.Experimental hematology · 2015Review
- Effects of topoisomerase inhibitors that induce DNA damage response on glucose metabolism and PI3K/Akt/mTOR signaling in multiple myeloma cells.American journal of cancer research · 2015Article
- Multifaceted roles of GSK-3 and Wnt/β-catenin in hematopoiesis and leukemogenesis: opportunities for therapeutic intervention.Leukemia · 2014Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Novel inhibitors of PI3K, Akt and mTOR have been developed recently, some of which have entered clinical trials. Although such compounds inhibit cell proliferation, their effects on cell survival, an important determinant of clinical response, are less distinct. Using a broad panel of myeloma cell lines and primary patient samples, we show that dual PI3K and mTOR inhibition can induce cell death. The effects are most marked in cells expressing the t(4;14) translocation, whereas t(11;14) cells are largely resistant. Using specific inhibitors of individual pathway components, we show that optimal induction of cell death requires inhibition of both PI3K and mTOR. This is due to a PI3K-independent component of mTOR activation downstream of the MAP kinase pathway. Novel mTOR kinase inhibitors, which block both TORC1 and TORC2 complexes thereby also reducing Akt activity, are less effective than dual PI3K/mTOR inhibitors because of feedback activation of PI3K signalling. Dual PI3K/mTOR inhibitors sensitise t(4;14) and t(14;16), but not t(11;14), expressing cells to the cytotoxic effects of dexamethasone. We have identified a robust cytogenetic biomarker for response to PI3K/mTOR inhibition--these results will inform the design and prioritisation of clinical studies with novel inhibitors in genetic subgroups of myeloma.
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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.