ArticleClinical and experimental immunology2018
Sorafenib paradoxically activates the RAS/RAF/ERK pathway in polyclonal human NK cells during expansion and thereby enhances effector functions in a dose- and time-dependent manner.
Article in Clinical and experimental immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Immunological characteristics of calmodulin-related genes in hepatocellular carcinoma and their potential for prognostic prediction and diagnostic applications.Journal of gastrointestinal oncology · 2026Article
- Integrative Machine Learning and Experimental Validation Identify MYBL2 as a Prognostic Biomarker and Therapeutic Target in Hepatocellular Carcinoma.Oncology research · 2026Article
- Assessment of the main signaling pathways involved in the combined therapy of hepatocellular carcinoma using Sorafenib and NK cells in xenograft mice model.Toxicology reports · 2025Article
- The role of exhausted natural killer cells in the immunopathogenesis and treatment of leukemia.Cell communication and signaling : CCS · 2024Review
- Sorafenib plus memory like natural killer cell combination therapy in hepatocellular carcinoma.American journal of cancer research · 2024Article
- CombinationThyroid : official journal of the American Thyroid Association · 2023Article
- Dual role of PID1 in regulating apoptosis induced by distinct anticancer-agents through AKT/Raf-1-dependent pathway in hepatocellular carcinoma.Cell death discovery · 2023Article
- Tyrosine kinase inhibitors as potential sensitizers of adoptive T cell therapy for hepatocellular carcinoma.Frontiers in immunology · 2023Review
- Applying a Gene Reversal Rate Computational Methodology to Identify Drugs for a Rare Cancer: Inflammatory Breast Cancer.Cancer informatics · 2023Article
- The effects of Sorafenib and Natural killer cell co-injection in combinational treatment of hepatocellular carcinoma; an in vivo approach.Pharmacological reports : PR · 2022Article
- Unleashing the power of NK cells in anticancer immunotherapy.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Adverse events of sorafenib in hepatocellular carcinoma treatment.American journal of cancer research · 2022Review
- [Regulatory effect of molecular targeted drugs on the immune system for liver cancer].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2021Review
- A phase I trial of sorafenib with whole brain radiotherapy (WBRT) in breast cancer patients with brain metastases and a correlative study of FLT-PET brain imaging.Breast cancer research and treatment · 2021Article
- Natural Killer Cells and Anti-Cancer Therapies: Reciprocal Effects on Immune Function and Therapeutic Response.Cancers · 2021Review
- OX40 as a novel target for the reversal of immune escape in colorectal cancer.American journal of translational research · 2021Review
- Combination of NK-based immunotherapy and sorafenib against hepatocellular carcinoma.American journal of cancer research · 2021Review
- Phenformin synergistically sensitizes liver cancer cells to sorafenib by downregulating CRAF/ERK and PI3K/AKT/mTOR pathways.American journal of translational research · 2021Article
- Combination of molecularly targeted therapies and immune checkpoint inhibitors in the new era of unresectable hepatocellular carcinoma treatment.Therapeutic advances in medical oncology · 2021Review
- RNAi-based small molecule repositioning reveals clinically approved urea-based kinase inhibitors as broadly active antivirals.PLoS pathogens · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural killer (NK) cells play a major role in host immunity against leukaemia and lymphoma. However, clinical trials applying NK cells have not been as efficient as hoped for. Patients treated with rapidly accelerated fibrosarcoma (RAF) inhibitors exhibit increased tumour infiltration by immune cells, suggesting that a combination of RAF inhibitors with immunotherapy might be beneficial. As mitogen-activated protein kinases (MAPKs) such as raf-1 proto-oncogene, serine/threonine kinase (CRAF) regulate NK cell functions, we performed an in-vitro investigation on the potential of clinically relevant short-acting tyrosine kinase inhibitors (TKIs) as potential adjuvants for NK cell therapy: NK cells from healthy human blood donors were thus treated with sorafenib, sunitinib or the pan-RAF inhibitor ZM336372 during ex-vivo expansion. Functional outcomes assessed after washout of the drugs included cytokine production, degranulation, cytotoxicity, apoptosis induction and signal transduction with/without target cell contact. Paradoxically, sorafenib enhanced NK cell effector functions in a time- and dose-dependent manner by raising the steady-state activation level. Of note, this did not lead to NK cell exhaustion, but enhanced activity against target cells such as K562 or Daudis mediated via the RAS/RAF/extracellular-regulated kinase (ERK) pathway, but not via protein kinase B (AKT). Our data will pave the path to develop a rationale for the considered use of RAF inhibitors such as sorafenib for pre-activation in NK cell-based adoptive immune therapy.
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