ArticleJournal of experimental & clinical cancer research : CR2019
Blockade of PDGFRβ circumvents resistance to MEK-JAK inhibition via intratumoral CD8
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Tyrosine hydroxylase as a therapeutic target: insights from adrenergic nerve and TNBC cell interactions.Journal of molecular medicine (Berlin, Germany) · 2026Article
- The dynamic role of platelets in cancer progression and their therapeutic implications.Nature reviews. Cancer · 2024Review
- Potential therapeutic targets of the JAK2/STAT3 signaling pathway in triple-negative breast cancer.Frontiers in oncology · 2024Review
- Copper chelation suppresses epithelial-mesenchymal transition by inhibition of canonical and non-canonical TGF-β signaling pathways in cancer.Cell & bioscience · 2023Article
- Pacritinib inhibits glucose consumption in squamous cell lung cancer cells by targeting FLT3.Scientific reports · 2023Article
- Targeting the effect of sofosbuvir on selective oncogenes expression level of hepatocellular carcinoma Ras/Raf/MEK/ERK pathway in Huh7 cell line.Saudi journal of biological sciences · 2022Article
- Diallyl disulfide and diallyl trisulfide in garlic as novel therapeutic agents to overcome drug resistance in breast cancer.Journal of pharmaceutical analysis · 2022Review
- Tumor Microenvironment: Key Players in Triple Negative Breast Cancer Immunomodulation.Cancers · 2021Review
- CX-5461 Enhances the Efficacy of APR-246 via Induction of DNA Damage and Replication Stress in Triple-Negative Breast Cancer.International journal of molecular sciences · 2021Article
- Tumor-infiltrating CD8Drug discovery today · 2021Review
- 'Off-the-shelf' allogeneic antigen-specific adoptive T-cell therapy for the treatment of multiple EBV-associated malignancies.Journal for immunotherapy of cancer · 2021Article
- Cep55 overexpression promotes genomic instability and tumorigenesis in mice.Communications biology · 2020Article
- Penetrable Nanoplatform for "Cold" Tumor Immune Microenvironment Reeducation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundDespite the increasing progress in targeted and immune based-directed therapies for other solid organ malignancies, currently there is no targeted therapy available for TNBCs. A number of mechanisms have been reported both in pre-clinical and clinical settings that involve inherent, acquired and adaptive resistance to small molecule inhibitors. Here, we demonstrated a novel resistance mechanism in TNBC cells mediated by PDGFRβ in response to JAK2 inhibition.
methodsMultiple in vitro (subG1, western blotting, immunofluorescence, RT-PCR, Immunoprecipitation), in vivo and publically available datasets were used.
resultsWe showed that TNBC cells exposed to MEK1/2-JAK2 inhibitors exhibit resistant colonies in anchorage-independent growth assays. Moreover, cells treated with various small molecule inhibitors including JAK2 promote PDGFRβ upregulation. Using publically available databases, we showed that patients expressing high PDGFRβ or its ligand PDGFB exhibit poor relapse-free survival upon chemotherapeutic treatment. Mechanistically we found that JAK2 expression controls steady state levels of PDGFRβ. Thus, co-blockade of PDGFRβ with JAK2 and MEK1/2 inhibitors completely eradicated resistant colonies in vitro. We found that triple-combined treatment had a significant impact on CD44
conclusionThese findings reveal a novel regulatory role of JAK2-mediated PDGFRβ proteolysis and provide an example of a PDGFRβ-mediated resistance mechanism upon specific target inhibition in TNBC.
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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.