ArticleJournal of the National Cancer Institute2015
PIM kinase inhibitor AZD1208 for treatment of MYC-driven prostate cancer.
Article in Journal of the National Cancer Institute, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 86 citations in OpenAlex.
- Macrophage PIM1 Drives Atherosclerosis by Enhancing Foam Cell Formation Via CD36.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Unraveling the role of host kinase PIM1 in Toxoplasma gondii infection: Implications for therapies.PLoS neglected tropical diseases · 2026Article
- In Silico Identification of Lepiotaprocerin C as a Promising PIM-1 Kinase Inhibitor: An Integrated Docking, Molecular Dynamics, MM/PBSA, QSAR, and ADMET Study.Bioinformatics and biology insights · 2026Article
- Akkermansia muciniphila-Derived N-Acetylspermidine Modulates the Localization of Intestinal α1,2-Fucosylated Proteins to Maintain Gut Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Low levels of tumor suppressor miR-3619 in plasma contribute to malignant outcomes and a target for nucleic acid therapy in esophageal cancer.Scientific reports · 2025Article
- PIM kinase inhibition counters resistance to radiotherapy and chemotherapy in human prostate cancer.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2025Article
- PIM1 induces hypoxia-related fibroblast senescence in a mouse model of stress urinary incontinence.PloS one · 2025Article
- Interactions between key genes and pathways in prostate cancer progression and therapy resistance.Frontiers in oncology · 2025Review
- Endothelial Pim3 kinase protects the vascular barrier during lung metastasis.Nature communications · 2024Article
- PIM1 kinase and its diverse substrate in solid tumors.Cell communication and signaling : CCS · 2024Review
- Pim Kinase Inhibitors Increase Gilteritinib Cytotoxicity in FLT3-ITD Acute Myeloid Leukemia Through GSK-3β Activation and c-Myc and Mcl-1 Proteasomal Degradation.Cancer research communications · 2024Article
- PIM3 Kinase: A Promising Novel Target in Solid Cancers.Cancers · 2024Review
- PIM Kinase Inhibitors as Novel Promising Therapeutic Scaffolds in Cancer Therapy.Current topics in medicinal chemistry · 2024Review
- Targeting Myc-driven stress addiction in colorectal cancer.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023Review
- The clinical and molecular characteristics of progressive hypothalamic/optic pathway pilocytic astrocytoma.Neuro-oncology · 2023Article
- When Just One Phosphate Is One Too Many: The Multifaceted Interplay between Myc and Kinases.International journal of molecular sciences · 2023Review
- Strategies to target the cancer driver MYC in tumor cells.Frontiers in oncology · 2023Review
- PIM2 Expression Induced by Proinflammatory Macrophages Suppresses Immunotherapy Efficacy in Hepatocellular Carcinoma.Cancer research · 2022Article
- PIM1/STAT3 axis: a potential co-targeted therapeutic approach in triple-negative breast cancer.Medical oncology (Northwood, London, England) · 2022Review
- Antiplatelet properties of Pim kinase inhibition are mediated through disruption of thromboxane A2 receptor signaling.Haematologica · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPIM1 kinase is coexpressed with c-MYC in human prostate cancers (PCs) and dramatically enhances c-MYC-induced tumorigenicity. Here we examine the effects of a novel oral PIM inhibitor, AZD1208, on prostate tumorigenesis and recurrence.
methodsA mouse c-MYC/Pim1-transduced tissue recombination PC model, Myc-CaP allografts, and human PC xenografts were treated with AZD1208 (n = 5-11 per group). Androgen-sensitive and castrate-resistant prostate cancer (CRPC) models were studied as well as the effects of hypoxia and radiation. RNA sequencing was used to analyze drug-induced gene expression changes. Results were analyzed with χ(2) test. Student's t test and nonparametric Mann-Whitney rank sum U Test. All statistical tests were two-sided.
resultsAZD1208 inhibited tumorigenesis in tissue recombinants, Myc-CaP, and human PC xenograft models. PIM inhibition decreased c-MYC/Pim1 graft growth by 54.3 ± 39% (P < .001), decreased cellular proliferation by 46 ± 14% (P = .016), and increased apoptosis by 326 ± 170% (P = .039). AZD1208 suppressed multiple protumorigenic pathways, including the MYC gene program. However, it also downregulated the p53 pathway. Hypoxia and radiation induced PIM1 in prostate cancer cells, and AZD1208 functioned as a radiation sensitizer. Recurrent tumors postcastration responded transiently to either AZD1208 or radiation treatment, and combination treatment resulted in more sustained inhibition of tumor growth. Cell lines established from recurrent, AZD1208-resistant tumors again revealed downregulation of the p53 pathway. Irradiated AZD1208-treated tumors robustly upregulated p53, providing a possible mechanistic explanation for the effectiveness of combination therapy. Finally, an AZD1208-resistant gene signature was found to be associated with biochemical recurrence in PC patients.
conclusionsPIM inhibition is a potential treatment for MYC-driven prostate cancers including CRPC, and its effectiveness may be enhanced by activators of the p53 pathway, such as radiation.
Indexed as
Identifiers
What OpenQuestion holds
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.