Evidence map›Paper›PMID 39978680›Full record

ArticleRadiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology2025

PIM kinase inhibition counters resistance to radiotherapy and chemotherapy in human prostate cancer.

Anne Rajkumar-Calkins, Vinay Sagar, Jian Wang, Shania Bailey, Philip Anderson, Sarki A Abdulkadir, Austin N Kirschner

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Article in Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Anne Rajkumar-CalkinsDepartment of Radiation Oncology, Vanderbilt University Medical Center, 2220 Pierce Ave, B1003 PRB, Nashville, TN 37232, USA; Department of Radiation Oncology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA.
Vinay SagarDepartment of Urology, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 676 N. St. Clair St., Arkes 2300, Chicago, IL 60611, USA.
Jian WangDepartment of Radiation Oncology, Vanderbilt University Medical Center, 2220 Pierce Ave, B1003 PRB, Nashville, TN 37232, USA.
Shania BaileyDepartment of Biological Sciences, Salisbury University, 1101 Camden Avenue, Salisbury, MD 21801, USA.
Philip AndersonDepartment of Biological Sciences, Salisbury University, 1101 Camden Avenue, Salisbury, MD 21801, USA.
Sarki A AbdulkadirDepartment of Urology and Pathology, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 303 E Superior St., Chicago, IL 60611, USA.
Austin N KirschnerDepartment of Radiation Oncology, Vanderbilt University Medical Center, 2220 Pierce Ave, B1003 PRB, Nashville, TN 37232, USA. Electronic address: austin.kirschner@vumc.org.

Funding

Vanderbilt Clinical Oncology Research Career Development ProgramK12CA090625 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Debra L. Friedman, Paula Jill Hurley · 2001 to 2026
$16.9M
NCI NIH HHS K12 CA090625
6 · The paper itself

Abstract

purposePIM kinases are associated with treatment resistance and poor prognosis in prostate cancer through roles in DNA damage response, cellular metabolism, proliferation, and survival. We hypothesized PIM inhibition addresses treatment resistance to radiotherapy and docetaxel in prostate cancer.

methodsPIM inhibition in prostate cancer cell lines was examined by phosphorylated H2AX and colony formations assays. In normal and castrated mice with prostate tumor xenografts, tumor growth was monitored with daily oral PIM inhibition +/- fractionated radiotherapy (RT) or docetaxel. Radiotherapy was given 30 Gy in 15 treatments, mimicking clinical conventional daily treatment over 3 weeks in a translational murine model system.

resultsPIM inhibition decreased radiotherapy-induced DNA-damage repair and decreased cell proliferation and survival. In mice, PIM inhibition increased the efficacy of both radiation and docetaxel to reduce tumor size in hormone-dependent and -independent xenografts. Xenografts showed altered gene expression changes, including downregulation of ribosomal pathways and upregulation of cardiomyocyte signaling pathways, due to PIM inhibition as analyzed by RNA-Seq. Immunostaining of multiple proteins, including COX-2 and MDM2, was altered by PIM inhibition.

conclusionsPIM inhibition addresses treatment resistance to docetaxel and radiotherapy in multiple prostate cancer models. Our data provide a strong rationale for testing PIM inhibitors in combination with standard therapies for treatment-resistant high-risk localized or metastatic prostate cancer in clinical trials.

Indexed as

Drug Resistance, NeoplasmProstatic NeoplasmsProtein Kinase InhibitorsProto-Oncogene Proteins c-pim-1Radiation ToleranceAnimalsAntineoplastic AgentsCell Line, TumorCell ProliferationDocetaxelHumansMaleMiceTaxoidsXenograft Model Antitumor AssaysAntineoplastic AgentsDocetaxelProtein Kinase InhibitorsProto-Oncogene Proteins c-pim-1proto-oncogene proteins pimTaxoidsDocetaxelModel organisms/animal models of cancerPIM kinaseProstate cancerRadiationRadiosensitization

Identifiers

PMID39978680
PMCPMC12851849

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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.