ArticleScience translational medicine2023
Targeting CCR7-PI3Kγ overcomes resistance to tyrosine kinase inhibitors in ALK-rearranged lymphoma.
Article in Science translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- Next-generation models for lymphoid malignancies: the rise of 3D culture systems in translational hematology.British journal of cancer · 2026Review
- Microfluidics for Blood Disorders and Hematological Disease Monitoring and Modeling.International journal of molecular sciences · 2026Review
- CCR7 orchestrates the malignant progression of memory B cells in MYC-overexpressing lymphoma.Cell death and differentiation · 2026Article
- Spatially decoding genotype-associated epigenetic landscapes in human lymphoma FFPE tissues via epi-Patho-DBiT.Nature communications · 2026Article
- Advances and updates in pediatric anaplastic large cell lymphoma.Blood advances · 2025Review
- BH3 mimetic drugs overcome the microenvironment-induced resistance to crizotinib in ALK+ anaplastic large cell lymphoma.Blood advances · 2025Article
- HDAC1 acts as a tumor suppressor in ALK-positive anaplastic large cell lymphoma: implications for HDAC inhibitor therapy.Leukemia · 2025Article
- Tumor-associated macrophages remodel the suppressive tumor immune microenvironment and targeted therapy for immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Review
- ALK in cancer: from function to therapeutic targeting.Nature reviews. Cancer · 2025Review
- Targeting PI3Kγ in cancer.Trends in cancer · 2025Review
- A patient-derived T cell lymphoma biorepository uncovers pathogenetic mechanisms and host-related therapeutic vulnerabilities.Cell reports. Medicine · 2025Article
- Review
- Anaplastic Lymphoma Kinase (ALK) Inhibitors Enhance Phagocytosis Induced by CD47 Blockade in Sensitive and Resistant ALK-Driven Malignancies.Biomedicines · 2024Article
- Injectable microgels containing genetically engineered bacteria for colon cancer therapy through programmed Chemokine expression.Materials today. Bio · 2024Article
- Recurrent somatic mutations of FAT family cadherins induce an aggressive phenotype and poor prognosis in anaplastic large cell lymphoma.British journal of cancer · 2024Article
- Review
- Mechanical forces amplify TCR mechanotransduction in T cell activation and function.Applied physics reviews · 2024Review
- Anaplastic lymphoma kinase inhibitors-a review of anticancer properties, clinical efficacy, and resistance mechanisms.Frontiers in pharmacology · 2023Review
Corrections and comments
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Authors and funding
36 authors at 15 institutions in 7 countries.
Funding
Abstract
Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) show potent efficacy in several ALK-driven tumors, but the development of resistance limits their long-term clinical impact. Although resistance mechanisms have been studied extensively in ALK-driven non-small cell lung cancer, they are poorly understood in ALK-driven anaplastic large cell lymphoma (ALCL). Here, we identify a survival pathway supported by the tumor microenvironment that activates phosphatidylinositol 3-kinase γ (PI3K-γ) signaling through the C-C motif chemokine receptor 7 (CCR7). We found increased PI3K signaling in patients and ALCL cell lines resistant to ALK TKIs. PI3Kγ expression was predictive of a lack of response to ALK TKI in patients with ALCL. Expression of CCR7, PI3Kγ, and PI3Kδ were up-regulated during ALK or STAT3 inhibition or degradation and a constitutively active PI3Kγ isoform cooperated with oncogenic ALK to accelerate lymphomagenesis in mice. In a three-dimensional microfluidic chip, endothelial cells that produce the CCR7 ligands CCL19/CCL21 protected ALCL cells from apoptosis induced by crizotinib. The PI3Kγ/δ inhibitor duvelisib potentiated crizotinib activity against ALCL lines and patient-derived xenografts. Furthermore, genetic deletion of CCR7 blocked the central nervous system dissemination and perivascular growth of ALCL in mice treated with crizotinib. Thus, blockade of PI3Kγ or CCR7 signaling together with ALK TKI treatment reduces primary resistance and the survival of persister lymphoma cells in ALCL.
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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.