ArticleOncogene2014
The PI3K inhibitor GDC-0941 combines with existing clinical regimens for superior activity in multiple myeloma.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 40 citations in OpenAlex.
- PI3K Signaling Pathway Inhibitor Affects Myeloma Cells in a Culture-Dependent Manner.Advanced pharmaceutical bulletin · 2025Article
- The ion channel TRPV5 regulates B-cell signaling and activation.Frontiers in immunology · 2024Article
- Combination Treatment Targeting mTOR and MAPK Pathways Has Synergistic Activity in Multiple Myeloma.Cancers · 2023Article
- Article
- The discrete roles of individual FOXO transcription factor family members in B-cell malignancies.Frontiers in immunology · 2023Review
- PI3K/mTOR Dual Inhibitor Pictilisib Stably Binds to Site I of Human Serum Albumin as Observed by Computer Simulation, Multispectroscopic, and Microscopic Studies.Molecules (Basel, Switzerland) · 2022Article
- GDC-0941 activates integrin linked kinase (ILK) expression to cause resistance to GDC-0941 in breast cancer by the tumor necrosis factor (TNF)-α signaling pathway.Bioengineered · 2022Article
- Inhibiting PI3K-AKT-mTOR Signaling in Multiple Myeloma-Associated Mesenchymal Stem Cells Impedes the Proliferation of Multiple Myeloma Cells.Frontiers in oncology · 2022Article
- Potential theranostics of circulating tumor cells and tumor-derived exosomes application in colorectal cancer.Cancer cell international · 2020Review
- High-Complexity shRNA Libraries and PI3 Kinase Inhibition in Cancer: High-Fidelity Synthetic Lethality Predictions.Cell reports · 2019Article
- Potent antitumor effect of combination therapy with sub-optimal doses of Akt inhibitors and pomalidomide plus dexamethasone in multiple myeloma.Oncology letters · 2018Article
- Lenalidomide improvement of cisplatin antitumor efficacy on triple-negative breast cancer cellsOncology letters · 2018Article
- Article
- Review
- PI3K as a Potential Therapeutic Target in Thymic Epithelial Tumors.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2016Article
- PIK3CA dependence and sensitivity to therapeutic targeting in urothelial carcinoma.BMC cancer · 2016Article
- Novel agents in the treatment of multiple myeloma: a review about the future.Journal of hematology & oncology · 2016Review
- Signaling Pathways and Emerging Therapies in Multiple Myeloma.Current hematologic malignancy reports · 2016Review
- Targeting RTK Signaling Pathways in Cancer.Cancers · 2015Review
- Small molecule inhibitor screen identifies synergistic activity of the bromodomain inhibitor CPI203 and bortezomib in drug resistant myeloma.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The phosphatidylinositol 3'-kinase (PI3K) pathway is dysregulated in multiple myeloma (MM); we therefore tested a highly selective class I PI3K inhibitor, GDC-0941, for anti-myeloma activity. Functional and mechanistic studies were first performed in MM cell lines, then extended to primary MM patient samples cultured in vitro. GDC-0941 was then assessed as a single agent and in various combinations in myeloma tumor xenograft models. We show p110 α and β are the predominant PI3K catalytic subunits in MM and that a highly selective class I PI3K inhibitor, GDC-0941, has robust activity as a single agent to induce cell cycle arrest and apoptosis of both MM cell lines and patient myeloma cells. Mechanistic studies revealed an induction of cell cycle arrest at G0/G1, with decreased phospho-FoxO1/3a levels, decreased cyclin D1 and c-myc expression, and an increase in the cell cycle inhibitor, p27kip. Induction of apoptosis correlated with increased expression of the pro-apoptotic BH3-only protein BIM, cleaved caspase 3 and cleaved poly (ADP-ribose) polymerase (PARP). In vitro, GDC-0941 synergized with dexamethasone (Dex) and lenalidomide (combination index values of 0.3-0.4 and 0.4-0.8, respectively); in vivo GDC-0941 has anti-myeloma activity and significantly increases the activity of the standard of care agents in several murine xenograft tumor models (additional tumor growth inhibition of 37-53% (Dex) and 22-72% (lenalidomide)). These data provide a clear therapeutic hypothesis for the inhibition of PI3K and provide a rationale for clinical development of GDC-0941 in 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.