ArticleProceedings of the National Academy of Sciences of the United States of America2021
Computational modeling identifies multitargeted kinase inhibitors as effective therapies for metastatic, castration-resistant prostate cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 29 citations in OpenAlex.
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- Biobank of genetically defined murine prostate cancer tumoroids uncovers oncogenic pathways and drug vulnerabilities driven by PTEN-loss.Cell reports methods · 2026Article
- A systems approach identifies MERTK as a therapeutic vulnerability in ZFTA-RELA-driven ependymomas.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Drug screening in 3D microtumors reveals DDR1/2-MAPK12-GLI1 as a vulnerability in cancer-associated fibroblasts.Cell reports. Medicine · 2025Article
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- A drug that induces the microRNA miR-124 enables differentiation of retinoic acid-resistant neuroblastoma cells.Science signaling · 2025Article
- Antiangiogenic Tyrosine Kinase Inhibitors have Differential Efficacy in Clear Cell Renal Cell Carcinoma in Bone.Cancer research communications · 2024Article
- Bone mimetic environments support engineering, propagation, and analysis of therapeutic response of patient-derived cells, ex vivo and in vivo.Acta biomaterialia · 2024Article
- Targeting prostate tumor low-molecular weight tyrosine phosphatase for oxidation-sensitizing therapy.Science advances · 2024Article
- A kinase to cytokine explorer to identify molecular regulators and potential therapeutic opportunities.eLife · 2024Article
- PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, relieves airway hyperresponsiveness, mucus hypersecretion and inflammation in a murine asthma model.Molecular medicine (Cambridge, Mass.) · 2023Article
- Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation.PLoS pathogens · 2023Article
- Computational drug discovery for castration-resistant prostate cancers through in vitro drug response modeling.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Subtype and Site Specific-Induced Metabolic Vulnerabilities in Prostate Cancer.Molecular cancer research : MCR · 2023Article
- Pharmacological approaches to understanding protein kinase signaling networks.Frontiers in pharmacology · 2023Review
- Effects of miR-103a-3p Targeted Regulation of TRIM66 Axis on Docetaxel Resistance and Glycolysis in Prostate Cancer Cells.Frontiers in genetics · 2021Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Castration-resistant prostate cancer (CRPC) is an advanced subtype of prostate cancer with limited therapeutic options. Here, we applied a systems-based modeling approach called kinome regularization (KiR) to identify multitargeted kinase inhibitors (KIs) that abrogate CRPC growth. Two predicted KIs, PP121 and SC-1, suppressed CRPC growth in two-dimensional in vitro experiments and in vivo subcutaneous xenografts. An ex vivo bone mimetic environment and in vivo tibia xenografts revealed resistance to these KIs in bone. Combining PP121 or SC-1 with docetaxel, standard-of-care chemotherapy for late-stage CRPC, significantly reduced tibia tumor growth in vivo, decreased growth factor signaling, and vastly extended overall survival, compared to either docetaxel monotherapy. These results highlight the utility of computational modeling in forming physiologically relevant predictions and provide evidence for the role of multitargeted KIs as chemosensitizers for late-stage, metastatic CRPC.
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