ArticleBlood2021
Activation of the MAPK pathway mediates resistance to PI3K inhibitors in chronic lymphocytic leukemia.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 61 citations in OpenAlex.
- Protein Profiles Predict Treatment Responses to the PI3K Inhibitor Umbralisib in Patients with Chronic Lymphocytic Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
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- BRAF Alterations in Chronic Lymphocytic Leukemia: Genomic Landscape, Co-Mutation Patterns, and Clinical Relevance.Current hematologic malignancy reports · 2026Review
- lncAPNet enables the deciphering of lncRNA-mRNA connections in patient transcriptomic data.Bioinformatics advances · 2026Article
- Evaluation of the Role of AID-Induced Mutagenesis in Resistance to B-Cell Receptor Pathway Inhibitors in Chronic Lymphocytic Leukemia.Current issues in molecular biology · 2025Article
- Effect of statins on IL-10 signaling and production by chronic lymphocytic leukemia cells.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Proteasome inhibition overcomes resistance to targeted therapies in B-cell malignancy models and in an index patient.Cell death & disease · 2025Article
- Multidrug Resistance: Are We Still Afraid of the Big Bad Wolf.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The Precision-Guided Use of PI3K Pathway Inhibitors for the Treatment of Solid Malignancies.Biomedicines · 2025Review
- Combinatorial screen of targeted agents with the PI3K inhibitors inavolisib, alpelisib, duvelisib, and copanlisib in multi-cell type tumor spheroids.SLAS discovery : advancing life sciences R & D · 2025Article
- Targeted therapies and resistance mechanisms in lymphoma: Current landscape and emerging solutions.Oncoscience · 2025Review
- Epigenetic Modeling of Jumping Translocations of 1q Heterochromatin in Acute Myeloid Leukemia After 5'-Azacytidine Treatment.Genes, chromosomes & cancer · 2024Article
- Bruton Tyrosine Kinase Inhibition Decreases Inflammation and Differentially Impacts Phagocytosis and Cellular Metabolism in Mouse- and Human-derived Myeloid Cells.ImmunoHorizons · 2024Article
- Integrative Analysis of Multi-Omics Data to Identify Deregulated Molecular Pathways and Druggable Targets in Chronic Lymphocytic Leukemia.Journal of personalized medicine · 2024Article
- Extracellular vesicles from type-2 macrophages increase the survival of chronic lymphocytic leukemia cells ex vivo.Cancer gene therapy · 2024Article
- Article
- Selective PI3Kδ inhibitor TYM-3-98 suppresses AKT/mTOR/SREBP1-mediated lipogenesis and promotes ferroptosis in KRAS-mutant colorectal cancer.Cell death & disease · 2024Article
- Insights into lenvatinib resistance: mechanisms, potential biomarkers, and strategies to enhance sensitivity.Medical oncology (Northwood, London, England) · 2024Review
- Molecular Targeting of the Phosphoinositide-3-Protein Kinase (PI3K) Pathway across Various Cancers.International journal of molecular sciences · 2024Review
- Mutations Detected in Real World Clinical Sequencing during BTK Inhibitor Treatment in CLL.Research square · 2024Article
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14 authors at 4 institutions in 1 country.
Funding
Abstract
Inhibitors of Bruton tyrosine kinase (BTK) and phosphatidylinositol 3-kinase δ (PI3Kδ) that target the B-cell receptor (BCR) signaling pathway have revolutionized the treatment of chronic lymphocytic leukemia (CLL). Mutations associated with resistance to BTK inhibitors have been identified, but limited data are available on mechanisms of resistance to PI3Kδ inhibitors. Here we present findings from longitudinal whole-exome sequencing of cells from patients with multiply relapsed CLL (N = 28) enrolled in trials of PI3K inhibitors. The nonresponder subgroup was characterized by baseline activating mutations in MAP2K1, BRAF, and KRAS genes in 60% of patients. PI3Kδ inhibition failed to inhibit ERK phosphorylation (pERK) in nonresponder CLL cells with and without mutations, whereas treatment with a MEK inhibitor rescued ERK inhibition. Overexpression of MAP2K1 mutants in vitro led to increased basal and inducible pERK and resistance to idelalisib. These data demonstrate that MAPK/ERK activation plays a key role in resistance to PI3Kδ inhibitors in CLL and provide a rationale for therapy with a combination of PI3Kδ and ERK inhibitors.
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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.