ArticleNeuro-oncology2016
Inhibition of DNA damage repair by the CDK4/6 inhibitor palbociclib delays irradiated intracranial atypical teratoid rhabdoid tumor and glioblastoma xenograft regrowth.
Open access · bronzeAbstract read
In one paragraph
Article in Neuro-oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed, 1 pooled it
5.2field-weighted citation impact, top 4% of its field
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
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.
- Molecular subgrouping of atypical teratoid/rhabdoid tumors-a reinvestigation and current consensus.Neuro-oncology · 2020Pooled it
- Phase II Trial of Palbociclib in Recurrent Retinoblastoma-Positive Anaplastic Oligodendroglioma: A Study from the Spanish Group for Research in Neuro-Oncology (GEINO).Targeted oncology · 2020Trial
- Phase-2 trial of palbociclib in adult patients with recurrent RB1-positive glioblastoma.Journal of neuro-oncology · 2018Trial
- Cyclin-Dependent Kinases 4 and 6 Inhibitors: An Emerging Therapeutic Framework from Growth Suppression to Tumor Clearance.ACS pharmacology & translational science · 2026Review
- Abemaciclib Inhibits Retinoblastoma Tumor Growth by Targeting CDK1/2.Investigative ophthalmology & visual science · 2026Article
- Preclinical Evaluation of the Efficacy of the Cyclin-Dependent Kinase Inhibitor Ribociclib in Combination with Letrozole against Patient-Derived Glioblastoma Cells.Molecular cancer therapeutics · 2026Article
- CDK4/6 inhibitors synergize with radiotherapy to prime the tumor microenvironment and enhance the antitumor effect of anti-PD-L1 immunotherapy in triple-negative breast cancer.Journal of biomedical science · 2025Article
- The regulatory role of CDK4/6 inhibitors in tumor immunity and the potential value of tumor immunotherapy (Review).International journal of molecular medicine · 2025Review
- Designing a time-dependent therapeutic strategy using CDK4/6 inhibitors in an intracranial ATRT model.Neuro-oncology · 2025Article
- CDK4/6 inhibitors in breast cancer therapy: mechanisms of drug resistance and strategies for treatment.Frontiers in pharmacology · 2025Review
- Radiosensitizing effects of CDK4/6 inhibitors in hormone receptor-positive and HER2-negative breast cancer mediated downregulation of DNA repair mechanism and NF-κB-signaling pathway.Translational oncology · 2024Article
- A kinome drug screen identifies multi-TKI synergies and ERBB2 signaling as a therapeutic vulnerability in MYC/TYR subgroup atypical teratoid rhabdoid tumors.Neuro-oncology · 2024Article
- DNA damage response in brain tumors: A Society for Neuro-Oncology consensus review on mechanisms and translational efforts in neuro-oncology.Neuro-oncology · 2024Review
- CDK4/6 inhibitor abemaciclib combined with low-dose radiotherapy enhances the anti-tumor immune response to PD-1 blockade by inflaming the tumor microenvironment in Rb-deficient small cell lung cancer.Translational lung cancer research · 2024Article
- GINS2 regulates temozolomide chemosensitivity via the EGR1/ECT2 axis in gliomas.Cell death & disease · 2024Article
- Safety of CDK4/6 Inhibitors Combined with Radiotherapy in Patients with Metastatic Breast Cancer: A Review of the Literature.Current oncology (Toronto, Ont.) · 2023Review
- FOXK1 regulates malignant progression and radiosensitivity through direct transcriptional activation of CDC25A and CDK4 in esophageal squamous cell carcinoma.Scientific reports · 2023Article
- Cellular senescence in the response of HRJournal of translational medicine · 2023Article
- Safety and Feasibility of Radiation Therapy Combined with CDK 4/6 Inhibitors in the Management of Advanced Breast Cancer.Cancers · 2023Article
- Atypical teratoid/rhabdoid tumour with CDK6 amplification in a child: a case report and literature review.Frontiers in pediatrics · 2023Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 1 institution in 1 country.
Rintaro HashizumeDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., A.Z., C.D.J., A.M.S., C.H.); Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., C.D.J.); Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (A.H.S., S.-Y.C.), Northwestern Brain Tumor Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.M.S., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois (A.P.M., C.D.J.); Department of Pediatrics, Division of Hematology/Oncology, Ann and Robert H. Lurie Children's Hospital, Chicago, Illinois (R.R.L., S.G.); Department of Neurological Surgery, University of California San Francisco, San Francisco, California (S.M., M.D.P.); Department of Pediatrics, University of California San Francisco, San Francisco, California (S.M.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Lombardi Cancer Center, Georgetown University, Washington, DC (T.W.).
Ali ZhangDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., A.Z., C.D.J., A.M.S., C.H.); Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., C.D.J.); Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (A.H.S., S.-Y.C.), Northwestern Brain Tumor Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.M.S., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois (A.P.M., C.D.J.); Department of Pediatrics, Division of Hematology/Oncology, Ann and Robert H. Lurie Children's Hospital, Chicago, Illinois (R.R.L., S.G.); Department of Neurological Surgery, University of California San Francisco, San Francisco, California (S.M., M.D.P.); Department of Pediatrics, University of California San Francisco, San Francisco, California (S.M.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Lombardi Cancer Center, Georgetown University, Washington, DC (T.W.).
Sabine MuellerDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., A.Z., C.D.J., A.M.S., C.H.); Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., C.D.J.); Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (A.H.S., S.-Y.C.), Northwestern Brain Tumor Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.M.S., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois (A.P.M., C.D.J.); Department of Pediatrics, Division of Hematology/Oncology, Ann and Robert H. Lurie Children's Hospital, Chicago, Illinois (R.R.L., S.G.); Department of Neurological Surgery, University of California San Francisco, San Francisco, California (S.M., M.D.P.); Department of Pediatrics, University of California San Francisco, San Francisco, California (S.M.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Lombardi Cancer Center, Georgetown University, Washington, DC (T.W.).
Michael D PradosDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., A.Z., C.D.J., A.M.S., C.H.); Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., C.D.J.); Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (A.H.S., S.-Y.C.), Northwestern Brain Tumor Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.M.S., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois (A.P.M., C.D.J.); Department of Pediatrics, Division of Hematology/Oncology, Ann and Robert H. Lurie Children's Hospital, Chicago, Illinois (R.R.L., S.G.); Department of Neurological Surgery, University of California San Francisco, San Francisco, California (S.M., M.D.P.); Department of Pediatrics, University of California San Francisco, San Francisco, California (S.M.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Lombardi Cancer Center, Georgetown University, Washington, DC (T.W.).
Rishi R LullaDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., A.Z., C.D.J., A.M.S., C.H.); Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., C.D.J.); Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (A.H.S., S.-Y.C.), Northwestern Brain Tumor Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.M.S., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois (A.P.M., C.D.J.); Department of Pediatrics, Division of Hematology/Oncology, Ann and Robert H. Lurie Children's Hospital, Chicago, Illinois (R.R.L., S.G.); Department of Neurological Surgery, University of California San Francisco, San Francisco, California (S.M., M.D.P.); Department of Pediatrics, University of California San Francisco, San Francisco, California (S.M.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Lombardi Cancer Center, Georgetown University, Washington, DC (T.W.).
Stewart GoldmanDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., A.Z., C.D.J., A.M.S., C.H.); Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., C.D.J.); Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (A.H.S., S.-Y.C.), Northwestern Brain Tumor Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.M.S., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois (A.P.M., C.D.J.); Department of Pediatrics, Division of Hematology/Oncology, Ann and Robert H. Lurie Children's Hospital, Chicago, Illinois (R.R.L., S.G.); Department of Neurological Surgery, University of California San Francisco, San Francisco, California (S.M., M.D.P.); Department of Pediatrics, University of California San Francisco, San Francisco, California (S.M.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Lombardi Cancer Center, Georgetown University, Washington, DC (T.W.).
Amanda M SaratsisDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., A.Z., C.D.J., A.M.S., C.H.); Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., C.D.J.); Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (A.H.S., S.-Y.C.), Northwestern Brain Tumor Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.M.S., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois (A.P.M., C.D.J.); Department of Pediatrics, Division of Hematology/Oncology, Ann and Robert H. Lurie Children's Hospital, Chicago, Illinois (R.R.L., S.G.); Department of Neurological Surgery, University of California San Francisco, San Francisco, California (S.M., M.D.P.); Department of Pediatrics, University of California San Francisco, San Francisco, California (S.M.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Lombardi Cancer Center, Georgetown University, Washington, DC (T.W.).
Andrew P MazarDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., A.Z., C.D.J., A.M.S., C.H.); Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., C.D.J.); Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (A.H.S., S.-Y.C.), Northwestern Brain Tumor Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.M.S., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois (A.P.M., C.D.J.); Department of Pediatrics, Division of Hematology/Oncology, Ann and Robert H. Lurie Children's Hospital, Chicago, Illinois (R.R.L., S.G.); Department of Neurological Surgery, University of California San Francisco, San Francisco, California (S.M., M.D.P.); Department of Pediatrics, University of California San Francisco, San Francisco, California (S.M.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Lombardi Cancer Center, Georgetown University, Washington, DC (T.W.).
Alexander H SteghDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., A.Z., C.D.J., A.M.S., C.H.); Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., C.D.J.); Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (A.H.S., S.-Y.C.), Northwestern Brain Tumor Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.M.S., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois (A.P.M., C.D.J.); Department of Pediatrics, Division of Hematology/Oncology, Ann and Robert H. Lurie Children's Hospital, Chicago, Illinois (R.R.L., S.G.); Department of Neurological Surgery, University of California San Francisco, San Francisco, California (S.M., M.D.P.); Department of Pediatrics, University of California San Francisco, San Francisco, California (S.M.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Lombardi Cancer Center, Georgetown University, Washington, DC (T.W.).
Shi-Yuan ChengDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., A.Z., C.D.J., A.M.S., C.H.); Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., C.D.J.); Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (A.H.S., S.-Y.C.), Northwestern Brain Tumor Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.M.S., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois (A.P.M., C.D.J.); Department of Pediatrics, Division of Hematology/Oncology, Ann and Robert H. Lurie Children's Hospital, Chicago, Illinois (R.R.L., S.G.); Department of Neurological Surgery, University of California San Francisco, San Francisco, California (S.M., M.D.P.); Department of Pediatrics, University of California San Francisco, San Francisco, California (S.M.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Lombardi Cancer Center, Georgetown University, Washington, DC (T.W.).
Craig HorbinskiDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., A.Z., C.D.J., A.M.S., C.H.); Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., C.D.J.); Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (A.H.S., S.-Y.C.), Northwestern Brain Tumor Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.M.S., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois (A.P.M., C.D.J.); Department of Pediatrics, Division of Hematology/Oncology, Ann and Robert H. Lurie Children's Hospital, Chicago, Illinois (R.R.L., S.G.); Department of Neurological Surgery, University of California San Francisco, San Francisco, California (S.M., M.D.P.); Department of Pediatrics, University of California San Francisco, San Francisco, California (S.M.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Lombardi Cancer Center, Georgetown University, Washington, DC (T.W.).
Daphne A Haas-KoganDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., A.Z., C.D.J., A.M.S., C.H.); Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., C.D.J.); Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (A.H.S., S.-Y.C.), Northwestern Brain Tumor Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.M.S., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois (A.P.M., C.D.J.); Department of Pediatrics, Division of Hematology/Oncology, Ann and Robert H. Lurie Children's Hospital, Chicago, Illinois (R.R.L., S.G.); Department of Neurological Surgery, University of California San Francisco, San Francisco, California (S.M., M.D.P.); Department of Pediatrics, University of California San Francisco, San Francisco, California (S.M.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Lombardi Cancer Center, Georgetown University, Washington, DC (T.W.).
Jann N SarkariaDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., A.Z., C.D.J., A.M.S., C.H.); Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., C.D.J.); Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (A.H.S., S.-Y.C.), Northwestern Brain Tumor Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.M.S., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois (A.P.M., C.D.J.); Department of Pediatrics, Division of Hematology/Oncology, Ann and Robert H. Lurie Children's Hospital, Chicago, Illinois (R.R.L., S.G.); Department of Neurological Surgery, University of California San Francisco, San Francisco, California (S.M., M.D.P.); Department of Pediatrics, University of California San Francisco, San Francisco, California (S.M.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Lombardi Cancer Center, Georgetown University, Washington, DC (T.W.).
Todd WaldmanDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., A.Z., C.D.J., A.M.S., C.H.); Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., C.D.J.); Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (A.H.S., S.-Y.C.), Northwestern Brain Tumor Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.M.S., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois (A.P.M., C.D.J.); Department of Pediatrics, Division of Hematology/Oncology, Ann and Robert H. Lurie Children's Hospital, Chicago, Illinois (R.R.L., S.G.); Department of Neurological Surgery, University of California San Francisco, San Francisco, California (S.M., M.D.P.); Department of Pediatrics, University of California San Francisco, San Francisco, California (S.M.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Lombardi Cancer Center, Georgetown University, Washington, DC (T.W.).
C David JamesDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., A.Z., C.D.J., A.M.S., C.H.); Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., C.D.J.); Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (A.H.S., S.-Y.C.), Northwestern Brain Tumor Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.M.S., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (R.H., R.R.L., S.G., A.P.M., A.H.S., S.-Y.C., C.H., C.D.J.); Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois (A.P.M., C.D.J.); Department of Pediatrics, Division of Hematology/Oncology, Ann and Robert H. Lurie Children's Hospital, Chicago, Illinois (R.R.L., S.G.); Department of Neurological Surgery, University of California San Francisco, San Francisco, California (S.M., M.D.P.); Department of Pediatrics, University of California San Francisco, San Francisco, California (S.M.); Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts (D.A.H.-K.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Lombardi Cancer Center, Georgetown University, Washington, DC (T.W.).
Northwestern University · US
Funding
Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9MProject 3: Spherical Nucleic Acids as Immunotherapeutic Agents for Prostate CancerU54CA199091 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI MIRKIN, CHAD A. · 2015 to 2019
$11.7MSpatio-Temporal Organization of Chromatin and Information Transfer in CancerU54CA193419 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI MARKO, JOHN F · 2015 to 2020
$10.4MPrecision Medicine For Pediatric Low-Grade GliomasR01NS091620 · NINDS · DANA-FARBER CANCER INST · PI HAAS-KOGAN, DAPHNE A., RESNICK, ADAM CAIN · 2015 to 2019
$2.6MGlioblastoma Phenotype Modulation Through miRNA Control of Wnt SignalingR01NS093843 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CHENG, SHI-YUAN · 2015 to 2019
$1.8MModulation of Oncogenic Signaling in GlioblastomasR01CA159811 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CHENG, SHI-YUAN · 2012 to 2016
$1.8MAutophagy Regulation of Glioblastoma Tumorigenesis and Responses to TherapyR01NS095634 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CHENG, SHI-YUAN · 2015 to 2019
$1.7MMechanisms of acquired temozolomide resistance in glioblastoma multiformeR01CA176830 · NCI · MAYO CLINIC ROCHESTER · PI SARKARIA, JANN N. · 2013 to 2017
$1.6MCdk4/6 Inhibitor Therapy for Glioblastoma MultiformeR01CA159467 · NCI · GEORGETOWN UNIVERSITY · PI JAMES, CHARLES DAVID, WALDMAN, TODD A · 2012 to 2016
$1.6MTargeting histone demethylase activity for the treatment of pediatric brainstem gliomaR01NS093079 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI HASHIZUME, RINTARO · 2015 to 2019
$1.5MThe Significance of Isocitrate Dehydrogenase Mutations in GliomasK08CA155764 · NCI · UNIVERSITY OF KENTUCKY · PI HORBINSKI, CRAIG MICHAEL · 2011 to 2015
$857kIdentification of Long Non-coding RNAs as Novel Biomarkers for Heterogeneous GlioblastomasR21CA209345 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CHENG, SHI-YUAN, ZHANG, WEI · 2016 to 2017
$365kNCI NIH HHS K08 CA155764NCI NIH HHS P30 CA060553NCI NIH HHS R01 CA159467NCI NIH HHS R01 CA159811NCI NIH HHS R01 CA176830NCI NIH HHS R21 CA209345NCI NIH HHS U54 CA193419NCI NIH HHS U54 CA199091NINDS NIH HHS R01 NS091620NINDS NIH HHS R01 NS093079NINDS NIH HHS R01 NS093843NINDS NIH HHS R01 NS095634
Abstract
backgroundRadiation therapy is the most commonly used postsurgical treatment for primary malignant brain tumors. Consequently, investigating the efficacy of chemotherapeutics combined with radiation for treating malignant brain tumors is of high clinical relevance. In this study, we examined the cyclin-dependent kinase 4/6 inhibitor palbociclib, when used in combination with radiation for treating human atypical teratoid rhabdoid tumor (ATRT) as well as glioblastoma (GBM).
methodsEvaluation of treatment antitumor activity in vitro was based upon results from cell proliferation assays, clonogenicity assays, flow cytometry, and immunocytochemistry for DNA double-strand break repair. Interpretation of treatment antitumor activity in vivo was based upon bioluminescence imaging, animal subject survival analysis, and staining of tumor sections for markers of proliferation and apoptosis.
resultsFor each of the retinoblastoma protein (RB)-proficient tumor models examined (2 ATRTs and 2 GBMs), one or more of the combination therapy regimens significantly (P < .05) outperformed both monotherapies with respect to animal subject survival benefit. Among the combination therapy regimens, concurrent palbociclib and radiation treatment and palbociclib treatment following radiation consistently outperformed the sequence in which radiation followed palbociclib treatment. In vitro investigation revealed that the concurrent use of palbociclib with radiation, as well as palbociclib following radiation, inhibited DNA double-strand break repair and promoted increased tumor cell apoptosis.
conclusionsOur results support further investigation and possible clinical translation of palbociclib as an adjuvant to radiation therapy for patients with malignant brain tumors that retain RB expression.
Indexed as
AnimalsAntineoplastic AgentsBrain NeoplasmsCell Line, TumorCell ProliferationChemoradiotherapyCombined Modality TherapyCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6DNA DamageDNA RepairFemaleGlioblastomaHeterograftsHumansMice, Inbred BALB CAntineoplastic AgentsCDK4 protein, humanCDK6 protein, humanCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6palbociclibPiperazinesPyridinesRetinoblastoma Proteinatypical teratoid rhabdoid tumorbioluminescence imagingglioblastomapalbociclibxenograft
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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.