ArticleNature cancer2024
Targeting a lineage-specific PI3Kɣ-Akt signaling module in acute myeloid leukemia using a heterobifunctional degrader molecule.
Article in Nature cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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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
15 citing papers in PubMed.
- Article
- Splicing-associated network PAK1-CLK1/4-SRRM1 is a vulnerability to overcome chemoresistance in human and mouse acute myeloid leukemia.Science translational medicine · 2026Article
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- An integrated multi-omics analysis reveals a core epigenetically-activated transcriptional network driving oncogenic signaling in acute myeloid leukemia.Discover oncology · 2026Article
- Exploiting tumor lineage features for precision cancer therapy.Trends in cancer · 2026Review
- Targeted protein degradation dismantles undruggable targets to reverse immune evasion and therapy resistance in cancer.Frontiers in immunology · 2026Review
- Integrating machine learning and multi-omics analysis to unveil key programmed cell death patterns and immunotherapy targets in kidney renal clear cell carcinoma.Scientific reports · 2025Article
- Aerobic Exercise and PI3K Inhibitor Ameliorate Obesity Cardiomyopathy by Alleviating Pyroptosis in Middle-Aged Mice.International journal of molecular sciences · 2025Article
- Design and in vitro evaluation of novel tetrazole derivatives of dianisidine as anticancer agents targeting Bcl-2 apoptosis regulator.Scientific reports · 2025Article
- Targeting PI3Kγ in cancer.Trends in cancer · 2025Review
- A metabolic synthetic lethality of phosphoinositide 3-kinase-driven cancer.Nature communications · 2025Article
- Recent advances in targeted degradation in the RAS pathway.Future medicinal chemistry · 2025Review
- Lycopene inhibits ER stress and apoptosis while modulating PI3K/AKT and enhancing antioxidant and anti-apoptotic proteins.PloS one · 2025Article
- Signaling pathways and advances in targeted therapy for adenomyosis.Frontiers in cell and developmental biology · 2025Review
- Noncanonical PI3Kγ signaling addiction is a therapeutic target in a subset of leukemias.Innovation (Cambridge (Mass.)) · 2024Review
Corrections and comments
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Authors and funding
35 authors.
Funding
Abstract
Dose-limiting toxicity poses a major limitation to the clinical utility of targeted cancer therapies, often arising from target engagement in nonmalignant tissues. This obstacle can be minimized by targeting cancer dependencies driven by proteins with tissue-restricted and/or tumor-restricted expression. In line with another recent report, we show here that, in acute myeloid leukemia (AML), suppression of the myeloid-restricted PIK3CG/p110γ-PIK3R5/p101 axis inhibits protein kinase B/Akt signaling and compromises AML cell fitness. Furthermore, silencing the genes encoding PIK3CG/p110γ or PIK3R5/p101 sensitizes AML cells to established AML therapies. Importantly, we find that existing small-molecule inhibitors against PIK3CG are insufficient to achieve a sustained long-term antileukemic effect. To address this concern, we developed a proteolysis-targeting chimera (PROTAC) heterobifunctional molecule that specifically degrades PIK3CG and potently suppresses AML progression alone and in combination with venetoclax in human AML cell lines, primary samples from patients with AML and syngeneic mouse models.
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What Socratic 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 Socratic graph.