ArticleNeuro-oncology2016
Phase I trial of p28 (NSC745104), a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in pediatric patients with recurrent or progressive central nervous system tumors: A Pediatric Brain Tumor Consortium Study.
Open access · bronzeAbstract readClinical Trial, Phase I
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 69 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 5% 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
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 135 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- Membrane-Traversing Peptides: Mechanistic Landscapes, Assays, and Applications.Chemical reviews · 2026Review
- Peptide-Based Delivery Systems: Selected Insights into Cell-Penetrating Peptides.ACS chemical neuroscience · 2026Review
- Therapeutic peptides and proteins: Status and developments in drug delivery.Journal of controlled release : official journal of the Controlled Release Society · 2026Review
- A multi-targeted therapeutic strategy for triple-negative breast cancer: the tumor-targeting peptide p28 enhances chemotherapy, induces apoptosis, crosses the blood-brain barrier, and suppresses metastasis.Apoptosis : an international journal on programmed cell death · 2026Article
- Suppression of mitochondrial energy production by a photosynthetic bacterial cupredoxin peptide inhibits tumor growth.Signal transduction and targeted therapy · 2026Article
- Multi-Omics Analysis of TYMS as a Prognostic Biomarker and Therapeutic Target for Lung Adenocarcinoma.Cancer medicine · 2026Article
- Microbiota in cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Possible Applications of Azurin, a Copper-Containing Protein, in Cancer Treatment: Prospects and Challenges.Current drug targets · 2026Review
- Improvement of DCIS resection using intraoperative imaging with ICG-p28.Scientific reports · 2025Article
- Cell-Mediated and Peptide-Based Delivery Systems: Emerging Frontiers in Targeted Therapeutics.Pharmaceutics · 2025Review
- Pandora's Box of AML: HowBiomedicines · 2025Review
- Ferroptosis-associated transcriptional factors in neurological diseases: molecular mechanisms and therapeutic prospects.Experimental & molecular medicine · 2025Review
- Intracellular redistribution of cell-penetrating peptide p28: A mechanism for enhanced anti-cancer activity.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- The Different Cellular Entry Routes for Drug Delivery Using Cell Penetrating Peptides.Biology of the cell · 2025Review
- Ameliorating vascular endothelial injury for lipolysacharide-induced via mitochondrial targeting function of octaarginine-modified essential oil from FructusChinese herbal medicines · 2025Article
- Azurin a potent anticancer and antimicrobial agent isolated from a novel Pseudomonas aeruginosa strain.Scientific reports · 2025Article
- Advances and prospects of cell-penetrating peptides in tumor immunotherapy.Scientific reports · 2025Review
- Applications of cell penetrating peptide-based drug delivery system in immunotherapy.Frontiers in immunology · 2025Review
- Bacteriocins in Cancer Treatment: Mechanisms and Clinical Potentials.Biomolecules · 2024Review
9 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 9 institutions in 1 country.
Rishi R LullaDivision of Hematology, Oncology, Neuro-Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois (R.R.L., S.G.); Division of Surgical Oncology, Department of Surgery, University of Illinois College of Medicine, Chicago, Illinois (T.Y., C.W.B.); Pharmacy Investigational Drug Service, University of Illinois Hospital and Health Sciences System, University of Illinois College of Pharmacy, Chicago, Illinois (L.B., M.P.); Department of Neurosurgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (I.F.P.); Departments of Neurology, Pediatrics, Neurosurgery, and Human Biology, Stanford University, Palo Alto, California (P.G.F.); Center for Neuroscience and Behavioral Medicine, Brain Tumor Institute, Children's National Health System, Department of Neurology and Pediatrics, The George Washington University, Washington, DC (R.J.P.); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, Weill Cornell Medical College, New York, New York (I.J.D.); Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California (G.D.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (S.W., A.O., J.M.B.); Department of Hematology-Oncology, Cincinnati Children's Hospital Medical Center, Neuro-Oncology Program, Cincinnati, Ohio (M.F.) rlulla@luriechildrens.org.
Stewart GoldmanDivision of Hematology, Oncology, Neuro-Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois (R.R.L., S.G.); Division of Surgical Oncology, Department of Surgery, University of Illinois College of Medicine, Chicago, Illinois (T.Y., C.W.B.); Pharmacy Investigational Drug Service, University of Illinois Hospital and Health Sciences System, University of Illinois College of Pharmacy, Chicago, Illinois (L.B., M.P.); Department of Neurosurgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (I.F.P.); Departments of Neurology, Pediatrics, Neurosurgery, and Human Biology, Stanford University, Palo Alto, California (P.G.F.); Center for Neuroscience and Behavioral Medicine, Brain Tumor Institute, Children's National Health System, Department of Neurology and Pediatrics, The George Washington University, Washington, DC (R.J.P.); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, Weill Cornell Medical College, New York, New York (I.J.D.); Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California (G.D.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (S.W., A.O., J.M.B.); Department of Hematology-Oncology, Cincinnati Children's Hospital Medical Center, Neuro-Oncology Program, Cincinnati, Ohio (M.F.).
Tohru YamadaDivision of Hematology, Oncology, Neuro-Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois (R.R.L., S.G.); Division of Surgical Oncology, Department of Surgery, University of Illinois College of Medicine, Chicago, Illinois (T.Y., C.W.B.); Pharmacy Investigational Drug Service, University of Illinois Hospital and Health Sciences System, University of Illinois College of Pharmacy, Chicago, Illinois (L.B., M.P.); Department of Neurosurgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (I.F.P.); Departments of Neurology, Pediatrics, Neurosurgery, and Human Biology, Stanford University, Palo Alto, California (P.G.F.); Center for Neuroscience and Behavioral Medicine, Brain Tumor Institute, Children's National Health System, Department of Neurology and Pediatrics, The George Washington University, Washington, DC (R.J.P.); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, Weill Cornell Medical College, New York, New York (I.J.D.); Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California (G.D.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (S.W., A.O., J.M.B.); Department of Hematology-Oncology, Cincinnati Children's Hospital Medical Center, Neuro-Oncology Program, Cincinnati, Ohio (M.F.).
Craig W BeattieDivision of Hematology, Oncology, Neuro-Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois (R.R.L., S.G.); Division of Surgical Oncology, Department of Surgery, University of Illinois College of Medicine, Chicago, Illinois (T.Y., C.W.B.); Pharmacy Investigational Drug Service, University of Illinois Hospital and Health Sciences System, University of Illinois College of Pharmacy, Chicago, Illinois (L.B., M.P.); Department of Neurosurgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (I.F.P.); Departments of Neurology, Pediatrics, Neurosurgery, and Human Biology, Stanford University, Palo Alto, California (P.G.F.); Center for Neuroscience and Behavioral Medicine, Brain Tumor Institute, Children's National Health System, Department of Neurology and Pediatrics, The George Washington University, Washington, DC (R.J.P.); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, Weill Cornell Medical College, New York, New York (I.J.D.); Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California (G.D.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (S.W., A.O., J.M.B.); Department of Hematology-Oncology, Cincinnati Children's Hospital Medical Center, Neuro-Oncology Program, Cincinnati, Ohio (M.F.).
Linda BresslerDivision of Hematology, Oncology, Neuro-Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois (R.R.L., S.G.); Division of Surgical Oncology, Department of Surgery, University of Illinois College of Medicine, Chicago, Illinois (T.Y., C.W.B.); Pharmacy Investigational Drug Service, University of Illinois Hospital and Health Sciences System, University of Illinois College of Pharmacy, Chicago, Illinois (L.B., M.P.); Department of Neurosurgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (I.F.P.); Departments of Neurology, Pediatrics, Neurosurgery, and Human Biology, Stanford University, Palo Alto, California (P.G.F.); Center for Neuroscience and Behavioral Medicine, Brain Tumor Institute, Children's National Health System, Department of Neurology and Pediatrics, The George Washington University, Washington, DC (R.J.P.); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, Weill Cornell Medical College, New York, New York (I.J.D.); Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California (G.D.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (S.W., A.O., J.M.B.); Department of Hematology-Oncology, Cincinnati Children's Hospital Medical Center, Neuro-Oncology Program, Cincinnati, Ohio (M.F.).
Michael PaciniDivision of Hematology, Oncology, Neuro-Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois (R.R.L., S.G.); Division of Surgical Oncology, Department of Surgery, University of Illinois College of Medicine, Chicago, Illinois (T.Y., C.W.B.); Pharmacy Investigational Drug Service, University of Illinois Hospital and Health Sciences System, University of Illinois College of Pharmacy, Chicago, Illinois (L.B., M.P.); Department of Neurosurgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (I.F.P.); Departments of Neurology, Pediatrics, Neurosurgery, and Human Biology, Stanford University, Palo Alto, California (P.G.F.); Center for Neuroscience and Behavioral Medicine, Brain Tumor Institute, Children's National Health System, Department of Neurology and Pediatrics, The George Washington University, Washington, DC (R.J.P.); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, Weill Cornell Medical College, New York, New York (I.J.D.); Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California (G.D.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (S.W., A.O., J.M.B.); Department of Hematology-Oncology, Cincinnati Children's Hospital Medical Center, Neuro-Oncology Program, Cincinnati, Ohio (M.F.).
Ian F PollackDivision of Hematology, Oncology, Neuro-Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois (R.R.L., S.G.); Division of Surgical Oncology, Department of Surgery, University of Illinois College of Medicine, Chicago, Illinois (T.Y., C.W.B.); Pharmacy Investigational Drug Service, University of Illinois Hospital and Health Sciences System, University of Illinois College of Pharmacy, Chicago, Illinois (L.B., M.P.); Department of Neurosurgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (I.F.P.); Departments of Neurology, Pediatrics, Neurosurgery, and Human Biology, Stanford University, Palo Alto, California (P.G.F.); Center for Neuroscience and Behavioral Medicine, Brain Tumor Institute, Children's National Health System, Department of Neurology and Pediatrics, The George Washington University, Washington, DC (R.J.P.); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, Weill Cornell Medical College, New York, New York (I.J.D.); Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California (G.D.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (S.W., A.O., J.M.B.); Department of Hematology-Oncology, Cincinnati Children's Hospital Medical Center, Neuro-Oncology Program, Cincinnati, Ohio (M.F.).
Paul Graham FisherDivision of Hematology, Oncology, Neuro-Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois (R.R.L., S.G.); Division of Surgical Oncology, Department of Surgery, University of Illinois College of Medicine, Chicago, Illinois (T.Y., C.W.B.); Pharmacy Investigational Drug Service, University of Illinois Hospital and Health Sciences System, University of Illinois College of Pharmacy, Chicago, Illinois (L.B., M.P.); Department of Neurosurgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (I.F.P.); Departments of Neurology, Pediatrics, Neurosurgery, and Human Biology, Stanford University, Palo Alto, California (P.G.F.); Center for Neuroscience and Behavioral Medicine, Brain Tumor Institute, Children's National Health System, Department of Neurology and Pediatrics, The George Washington University, Washington, DC (R.J.P.); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, Weill Cornell Medical College, New York, New York (I.J.D.); Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California (G.D.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (S.W., A.O., J.M.B.); Department of Hematology-Oncology, Cincinnati Children's Hospital Medical Center, Neuro-Oncology Program, Cincinnati, Ohio (M.F.).
Roger J PackerDivision of Hematology, Oncology, Neuro-Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois (R.R.L., S.G.); Division of Surgical Oncology, Department of Surgery, University of Illinois College of Medicine, Chicago, Illinois (T.Y., C.W.B.); Pharmacy Investigational Drug Service, University of Illinois Hospital and Health Sciences System, University of Illinois College of Pharmacy, Chicago, Illinois (L.B., M.P.); Department of Neurosurgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (I.F.P.); Departments of Neurology, Pediatrics, Neurosurgery, and Human Biology, Stanford University, Palo Alto, California (P.G.F.); Center for Neuroscience and Behavioral Medicine, Brain Tumor Institute, Children's National Health System, Department of Neurology and Pediatrics, The George Washington University, Washington, DC (R.J.P.); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, Weill Cornell Medical College, New York, New York (I.J.D.); Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California (G.D.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (S.W., A.O., J.M.B.); Department of Hematology-Oncology, Cincinnati Children's Hospital Medical Center, Neuro-Oncology Program, Cincinnati, Ohio (M.F.).
Ira J DunkelDivision of Hematology, Oncology, Neuro-Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois (R.R.L., S.G.); Division of Surgical Oncology, Department of Surgery, University of Illinois College of Medicine, Chicago, Illinois (T.Y., C.W.B.); Pharmacy Investigational Drug Service, University of Illinois Hospital and Health Sciences System, University of Illinois College of Pharmacy, Chicago, Illinois (L.B., M.P.); Department of Neurosurgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (I.F.P.); Departments of Neurology, Pediatrics, Neurosurgery, and Human Biology, Stanford University, Palo Alto, California (P.G.F.); Center for Neuroscience and Behavioral Medicine, Brain Tumor Institute, Children's National Health System, Department of Neurology and Pediatrics, The George Washington University, Washington, DC (R.J.P.); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, Weill Cornell Medical College, New York, New York (I.J.D.); Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California (G.D.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (S.W., A.O., J.M.B.); Department of Hematology-Oncology, Cincinnati Children's Hospital Medical Center, Neuro-Oncology Program, Cincinnati, Ohio (M.F.).
Girish DhallDivision of Hematology, Oncology, Neuro-Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois (R.R.L., S.G.); Division of Surgical Oncology, Department of Surgery, University of Illinois College of Medicine, Chicago, Illinois (T.Y., C.W.B.); Pharmacy Investigational Drug Service, University of Illinois Hospital and Health Sciences System, University of Illinois College of Pharmacy, Chicago, Illinois (L.B., M.P.); Department of Neurosurgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (I.F.P.); Departments of Neurology, Pediatrics, Neurosurgery, and Human Biology, Stanford University, Palo Alto, California (P.G.F.); Center for Neuroscience and Behavioral Medicine, Brain Tumor Institute, Children's National Health System, Department of Neurology and Pediatrics, The George Washington University, Washington, DC (R.J.P.); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, Weill Cornell Medical College, New York, New York (I.J.D.); Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California (G.D.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (S.W., A.O., J.M.B.); Department of Hematology-Oncology, Cincinnati Children's Hospital Medical Center, Neuro-Oncology Program, Cincinnati, Ohio (M.F.).
Shengjie WuDivision of Hematology, Oncology, Neuro-Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois (R.R.L., S.G.); Division of Surgical Oncology, Department of Surgery, University of Illinois College of Medicine, Chicago, Illinois (T.Y., C.W.B.); Pharmacy Investigational Drug Service, University of Illinois Hospital and Health Sciences System, University of Illinois College of Pharmacy, Chicago, Illinois (L.B., M.P.); Department of Neurosurgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (I.F.P.); Departments of Neurology, Pediatrics, Neurosurgery, and Human Biology, Stanford University, Palo Alto, California (P.G.F.); Center for Neuroscience and Behavioral Medicine, Brain Tumor Institute, Children's National Health System, Department of Neurology and Pediatrics, The George Washington University, Washington, DC (R.J.P.); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, Weill Cornell Medical College, New York, New York (I.J.D.); Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California (G.D.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (S.W., A.O., J.M.B.); Department of Hematology-Oncology, Cincinnati Children's Hospital Medical Center, Neuro-Oncology Program, Cincinnati, Ohio (M.F.).
Arzu OnarDivision of Hematology, Oncology, Neuro-Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois (R.R.L., S.G.); Division of Surgical Oncology, Department of Surgery, University of Illinois College of Medicine, Chicago, Illinois (T.Y., C.W.B.); Pharmacy Investigational Drug Service, University of Illinois Hospital and Health Sciences System, University of Illinois College of Pharmacy, Chicago, Illinois (L.B., M.P.); Department of Neurosurgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (I.F.P.); Departments of Neurology, Pediatrics, Neurosurgery, and Human Biology, Stanford University, Palo Alto, California (P.G.F.); Center for Neuroscience and Behavioral Medicine, Brain Tumor Institute, Children's National Health System, Department of Neurology and Pediatrics, The George Washington University, Washington, DC (R.J.P.); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, Weill Cornell Medical College, New York, New York (I.J.D.); Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California (G.D.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (S.W., A.O., J.M.B.); Department of Hematology-Oncology, Cincinnati Children's Hospital Medical Center, Neuro-Oncology Program, Cincinnati, Ohio (M.F.).
James M BoyettDivision of Hematology, Oncology, Neuro-Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois (R.R.L., S.G.); Division of Surgical Oncology, Department of Surgery, University of Illinois College of Medicine, Chicago, Illinois (T.Y., C.W.B.); Pharmacy Investigational Drug Service, University of Illinois Hospital and Health Sciences System, University of Illinois College of Pharmacy, Chicago, Illinois (L.B., M.P.); Department of Neurosurgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (I.F.P.); Departments of Neurology, Pediatrics, Neurosurgery, and Human Biology, Stanford University, Palo Alto, California (P.G.F.); Center for Neuroscience and Behavioral Medicine, Brain Tumor Institute, Children's National Health System, Department of Neurology and Pediatrics, The George Washington University, Washington, DC (R.J.P.); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, Weill Cornell Medical College, New York, New York (I.J.D.); Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California (G.D.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (S.W., A.O., J.M.B.); Department of Hematology-Oncology, Cincinnati Children's Hospital Medical Center, Neuro-Oncology Program, Cincinnati, Ohio (M.F.).
Maryam FouladiDivision of Hematology, Oncology, Neuro-Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois (R.R.L., S.G.); Division of Surgical Oncology, Department of Surgery, University of Illinois College of Medicine, Chicago, Illinois (T.Y., C.W.B.); Pharmacy Investigational Drug Service, University of Illinois Hospital and Health Sciences System, University of Illinois College of Pharmacy, Chicago, Illinois (L.B., M.P.); Department of Neurosurgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (I.F.P.); Departments of Neurology, Pediatrics, Neurosurgery, and Human Biology, Stanford University, Palo Alto, California (P.G.F.); Center for Neuroscience and Behavioral Medicine, Brain Tumor Institute, Children's National Health System, Department of Neurology and Pediatrics, The George Washington University, Washington, DC (R.J.P.); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, Weill Cornell Medical College, New York, New York (I.J.D.); Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California (G.D.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (S.W., A.O., J.M.B.); Department of Hematology-Oncology, Cincinnati Children's Hospital Medical Center, Neuro-Oncology Program, Cincinnati, Ohio (M.F.).
Children's Hospital of Los Angeles · USCornell University · USUniversity of Pittsburgh · USChildren's Center · USChildren's National · USNorthwestern University · USUniversity of Illinois Chicago · USUniversity of Illinois Hospital & Health Sciences System · USUniversity of Southern California · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MTumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9MPediatric Brain Tumor Consortium (PBTC)UM1CA081457 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Ira J Dunkel, Arzu Onar-Thomas · 2014 to 2026
$41.4MThe Pediatric Brain Tumor Consortium (PBTC)U01CA081457 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI BOYETT, JAMES MILFORD · 1999 to 2013
$29.2MNCI NIH HHS P30 CA008748NCI NIH HHS P30 CA060553NCI NIH HHS U01 CA081457NCI NIH HHS UM1 CA081457
Abstract
backgroundp53 is a promising target in human cancer. p28 is a cell-penetrating peptide that preferentially enters cancer cells and binds to both wild-type and mutant p53 protein, inhibiting COP1-mediated ubiquitination and proteasomal degradation. This results in increased levels of p53, which induces cell cycle arrest at G2/M. We conducted a phase I study to determine the maximum-tolerated dose (MTD) and describe the dose-limiting toxicities (DLTs) and pharmacokinetics (PKs) of p28 in children.
methodsChildren aged 3-21 years with recurrent or progressive central nervous system tumors were eligible. Intravenous p28 was administered 3 times weekly for 4 consecutive weeks of a 6-week cycle at 4.16 mg/kg/dose (the adult recommended phase II dose) using a rolling-6 study design. Expression status of p53 was characterized by immunohistochemistry, and serum PK parameters were established on the second dose.
resultsOf the 18 eligible patients enrolled in the study, 12 completed the DLT monitoring period and were evaluable for toxicity. p28 was well-tolerated; 7 participants received ≥2 courses, and the most common adverse event attributed to the drug was transient grade 1 infusion-related reaction. PK analysis revealed a profile similar to adults; however, an increased area under the curve was observed in pediatric patients. High p53 expression in tumor cell nuclei was observed in 6 of 12 available tissue samples. There were no objective responses; 2 participants remained stable on the study for >4 cycles.
conclusionsThis phase I study demonstrated that p28 is well-tolerated in children with recurrent CNS malignancies at the adult recommended phase II dose.
Indexed as
AdolescentAdultAntineoplastic AgentsAzurinCentral Nervous System NeoplasmsChildChild, PreschoolDose-Response Relationship, DrugFemaleFollow-Up StudiesHumansMaleMaximum Tolerated DoseNeoplasm Recurrence, LocalNeoplasm StagingPeptide FragmentsAntineoplastic AgentsAzurinazurin (50-77)Peptide FragmentsTumor Suppressor Protein p53azurincentral nervous system tumorsp28pediatricphase I.
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