ArticleEndocrine-related cancer2019
MAPK- and AKT-activated thyroid cancers are sensitive to group I PAK inhibition.
Article in Endocrine-related cancer, 2019. 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, 25 citations in OpenAlex.
- RAC1 signaling in polyploid giant cancer cells: Implications for tumorigenesis and therapy resistance.Cancer letters · 2026Review
- Computational Identification of New Dual PAK4 and NAMPT Inhibitors.International journal of molecular sciences · 2026Article
- Comprehensive analysis of cuproptosis-related lncRNAs in immunotherapy response and prognosis in papillary thyroid cancer.Gland surgery · 2026Article
- Investigating PAK inhibition in combination with PD-1 blockade to enhance cytotoxic CD8+ T cell-mediated killing and suppress invasion of ovarian cancer cells.British journal of cancer · 2026Article
- Unravelling SLC7 family members in thyroid cancer and translational barriers.American journal of cancer research · 2026Review
- The Role of the p21-Activated Kinase Family in Tumor Immunity.International journal of molecular sciences · 2025Review
- TERT promoter mutations contribute to adverse clinical outcomes and poor prognosis in radioiodine refractory differentiated thyroid cancer.Scientific reports · 2024Article
- Hypermethylation of microRNA-497-3p contributes to progression of thyroid cancer through activation of PAK1/β-catenin.Cell biology and toxicology · 2023Article
- CircNDST1 promotes papillary thyroid cancer progression via its interaction with CSNK2A1 to activate the PI3K-Akt pathway and epithelial-mesenchymal transition.Journal of endocrinological investigation · 2023Article
- Hyperactivation of p21-Activated Kinases in Human Cancer and Therapeutic Sensitivity.Biomedicines · 2023Review
- Development and Utility of a PAK1-Selective Degrader.Journal of medicinal chemistry · 2022Article
- Non-genomic activation of the AKT-mTOR pathway by the mitochondrial stress response in thyroid cancer.Oncogene · 2022Article
- Circular RNA hsa_circ_0004396 acts as a sponge of miR-615-5p to promote non-small cell lung cancer progression and radioresistance through the upregulation of P21-Activated Kinase 1.Journal of clinical laboratory analysis · 2022Article
- Long non-coding ROR promotes the progression of papillary thyroid carcinoma through regulation of the TESC/ALDH1A1/TUBB3/PTEN axis.Cell death & disease · 2022Article
- Roles of Cadherin2 in Thyroid Cancer.Frontiers in oncology · 2022Article
- Review
- Article
- New Horizons: Emerging Therapies and Targets in Thyroid Cancer.The Journal of clinical endocrinology and metabolism · 2021Review
- p21-Activated Kinases in Thyroid Cancer.Endocrinology · 2020Review
- Targeting Rho GTPase Signaling Networks in Cancer.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The number of individuals who succumb to thyroid cancer has been increasing and those who are refractory to standard care have limited therapeutic options, highlighting the importance of developing new treatments for patients with aggressive forms of the disease. Mutational activation of MAPK signaling, through BRAF and RAS mutations and/or gene rearrangements, and activation of PI3K signaling, through mutational activation of PIK3CA or loss of PTEN, are well described in aggressive thyroid cancer. We previously reported overactivation and overexpression of p21-activated kinases (PAKs) in aggressive human thyroid cancer invasive fronts and determined that PAK1 functionally regulated thyroid cancer cell migration. We reported mechanistic crosstalk between the MAPK and PAK pathways that are BRAF-dependent but MEK independent, suggesting that PAK and MEK inhibition might be synergistic. In the present study, we tested this hypothesis. Pharmacologic inhibition of group I PAKs using two PAK kinase inhibitors, G-5555 or FRAX1036, reduced thyroid cancer cell viability, cell cycle progression and migration and invasion, with greater potency for G-5555. Combination of G-5555 with vemurafenib was synergistic in BRAFV600E-mutated thyroid cancer cell lines. Finally, G-5555 restrained thyroid size of BRAFV600E-driven murine papillary thyroid cancer by >50% (P < 0.0001) and reduced carcinoma formation (P = 0.0167), despite maintenance of MAPK activity. Taken together, these findings suggest both that group I PAKs may be a new therapeutic target for thyroid cancer and that PAK activation is functionally important for BRAFV600E-mediated thyroid cancer development.
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