The pediatric preclinical testing program: Description of models and early testing results
Abstract
Background: The Pediatric Preclinical Testing Program (PPTP) is an initiative supported by the National Cancer Institute (NCI) to identify novel therapeutic agents that may have significant activity against childhood cancers. The PPTP has established panels of childhood cancer xenografts and cell lines to be used for in vivo and in vitro testing. These include panels for Wilms tumor, sarcomas (rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma), neuroblastoma, brain tumors (glioblastoma, ependymoma, and medulloblastoma), rhabdoid tumors (CNS and renal), and acute lymphoblastic leukemia (ALL). Here, we describe the characteristics of the in vivo tumor panels and report results for the in vivo evaluation of two standard agents, vincristine and cyclophosphamide. Procedures: Solid tumors were grown subcutaneously in immune‐deficient mice and tumor dimensions were measured weekly. ALL xenografts were inoculated intravenously and human CD45‐positive cells were enumerated weekly. Results: Vincristine‐induced objective responses in 6 of 24 (25%) and cyclophosphamide‐induced objective responses in 18 of 28 (64%) solid tumor models. Comparable assessments of high levels of activity for these two agents were obtained using a tumor growth delay (TGD) measure. Both agents induced regressions in each of the ALL models evaluated. Conclusions: We have established 51 solid tumor and 10 ALL in vivo models. The models identify vincristine and cyclophosphamide as having broad‐spectrum activity. The PPTP tumor panels appear to generally recapitulate the activity of these agents against specific childhood cancers and to have the potential for identifying novel agents having significant clinical activity. Pediatr Blood Cancer 2007;49:928–940. Published 2006 Wiley‐Liss, Inc.
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PDX model systems are valuable in basic science and personalized medicine because they have clinical and molecular features representative of human disease.
“These PDX model systems are of particular value in both basic science and potentially personalized medicine research 180,183,222 as they have clinical and molecular features that are quite representative of the human disease 223,224,225,226 .”
From Osteosarcoma (2022) · cites this paper as [224]
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- Authors
- Houghton, P. J., Morton, C. L., Tucker, C., Payne, D., Favours, E., Cole, C., Gorlick, R., Kolb, E. A., Zhang, W., Lock, R., Carol, H., Tajbakhsh, M., Reynolds, C. P., Maris, J. M., Courtright, J., Keir, S. T., Friedman, H. S., Stopford, C., Zeidner, J., Wu, J., Liu, T., Billups, C. A., Khan, J., Ansher, S., Zhang, J., & Smith, M. A.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Children's Hospital at Montefiore (US)
- Children's Cancer Institute Australia (AU)
- Children's Hospital Los Angeles (US)
- Children's Hospital of Philadelphia (US)
- Duke Medical Center (US)
- National Cancer Institute (US)
- Corresponding author
- Houghton, Peter J.
- ORCID
- Venue
- Pediatric Blood & Cancer
- Publisher
- Wiley
- Published
- 2006-10-25
- Volume
- 49
- Issue
- 7
- Pages
- 928-940
- ISSN
- 1545-5009 (ISSN-L)
- 1545-5017
- OpenAlex
- W1571073982
- Cited by
- 480
- References
- 39
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 16 · 2023: 35 · 2022: 18 · 2021: 15 · 2020: 30 · 2019: 32 · 2018: 19 · 2017: 19 · 2016: 27 · 2015: 25 · 2014: 31 · 2013: 33 · 2012: 24
- FWCI
- 14.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pediatric Blood & Cancer (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (NO1-CM-42216)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Keywords
- childhood cancer, xenograft tumor model, solid tumor xenografts, vincristine, cyclophosphamide, tumor growth inhibition, Wilms tumor, rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, neuroblastoma, brain tumors, rhabdoid tumor, drug screening
- MeSH terms
- Animals, Cyclophosphamide, Disease Models, Animal, Drug Administration Schedule, Female, Humans, Injections, Intraperitoneal, Mice, Inbred BALB C, Mice, Nude, Neoplasms, Vincristine, Mice, SCID, Mice, Inbred NOD, Treatment Outcome, Disease-Free Survival, Xenograft Model Antitumor Assays, Cell Proliferation, Mice
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