ArticleNature cancer2022
P2RY2-AKT activation is a therapeutically actionable consequence of XPO1 inhibition in acute myeloid leukemia.
Article in Nature cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 39 citations in OpenAlex.
- Long-term follow-up of efficacy and safety of selinexor maintenance treatment in patients with TP53wt advanced or recurrent endometrial cancer: A subgroup analysis of the ENGOT-EN5/GOG-3055/SIENDO study.Gynecologic oncology · 2024Trial
- XPO1: From basic research to clinical treatment (Review).Oncology reports · 2026Review
- CD73 inhibitor enhances the antitumor activity of selinexor in multiple myeloma by restoring the activation of CD8Cancer gene therapy · 2026Article
- Targeting the nuclear export receptor exportin-1 in acute myeloid leukaemia: From biology to clinical translation.Clinical and translational medicine · 2026Review
- CCT3-mediated regulation of XPO1/RB1 axis stability promotes cellular senescence and tumor progression in clear cell renal carcinoma.iScience · 2026Article
- The Art of Domesticating Proteins: How Cancer Cells Adapt to Therapeutic and Environmental Stressors.International journal of molecular sciences · 2026Review
- Enhancing Anti-Tumor Effects of Engineered Extracellular Vesicles via Endocytosis Route Switching and Interferon Response Suppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- KBTBD11 loss promotes AKT hyperactivation and therapeutic vulnerability in prostate cancer.Oncogene · 2025Article
- Disease-specific epigenetic deregulation of enhancers, transposons, and polycomb targets in acute promyelocytic leukemia.Genome medicine · 2025Article
- Integrative multi-omic analysis of NLRP3 inflammasome dysregulation and subtyping for personalized treatment in acute myeloid leukemia.Discover oncology · 2025Article
- Positive Feedback Regulation between KLF5 and XPO1 Promotes Cell Cycle Progression of Basal like Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Comprehensive insights into potential roles of purinergic P2 receptors on diseases: Signaling pathways involved and potential therapeutics.Journal of advanced research · 2025Review
- XPO1/Exportin-1 in Acute Myelogenous Leukemia; Biology and Therapeutic Targeting.Biomolecules · 2025Review
- XPO1-inhibitor Selinexor induces MGMT expression by activating PKA-CREB signaling inFrontiers in oncology · 2025Article
- Advances in the application of patient-derived xenograft models in acute leukemia resistance.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Selinexor in acute myeloid leukemia: therapeutic applications and current challenges.Frontiers in pharmacology · 2025Review
- Altered RNA export by SF3B1 mutants confers sensitivity to nuclear export inhibition.Leukemia · 2024Article
- Exportin 1 governs the immunosuppressive functions of myeloid-derived suppressor cells in tumors through ERK1/2 nuclear export.Cellular & molecular immunology · 2024Article
- Targeting a lineage-specific PI3Kɣ-Akt signaling module in acute myeloid leukemia using a heterobifunctional degrader molecule.Nature cancer · 2024Article
- Monocytic Differentiation in Acute Myeloid Leukemia Cells: Diagnostic Criteria, Biological Heterogeneity, Mitochondrial Metabolism, Resistance to and Induction by Targeted Therapies.International journal of molecular sciences · 2024Review
Corrections and comments
- Commented on by
Authors and funding
33 authors at 6 institutions in 2 countries.
Funding
Abstract
Selinexor is a first-in-class inhibitor of the nuclear exportin XPO1 that was recently approved by the US Food and Drug Administration for the treatment of multiple myeloma and diffuse large B-cell lymphoma. In relapsed/refractory acute myeloid leukemia (AML), selinexor has shown promising activity, suggesting that selinexor-based combination therapies may have clinical potential. Here, motivated by the hypothesis that selinexor's nuclear sequestration of diverse substrates imposes pleiotropic fitness effects on AML cells, we systematically catalog the pro- and anti-fitness consequences of selinexor treatment. We discover that selinexor activates PI3Kγ-dependent AKT signaling in AML by upregulating the purinergic receptor P2RY2. Inhibiting this axis potentiates the anti-leukemic effects of selinexor in AML cell lines, patient-derived primary cultures and multiple mouse models of AML. In a syngeneic, MLL-AF9-driven mouse model of AML, treatment with selinexor and ipatasertib outperforms both standard-of-care chemotherapy and chemotherapy with selinexor. Together, these findings establish drug-induced P2RY2-AKT signaling as an actionable consequence of XPO1 inhibition in AML.
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.