NDLI: PATIENT-DERIVED XENOGRAFTS MIRROR THE PROTEOMIC PROFILE OF HUMAN GLIOBLASTOMA: IMPLICATIONS FOR PERSONALIZED DRUG DEVELOPMENT

Content Provider	PubMed Central
Author	Kwatra, Madan M. Brown, Kristine E. Chagoya, Gustavo Keir, Stephen T. Bigner, Darell D. Sampson, John H.
Copyright Year	2014
Abstract	BACKGROUND: (blind field). METHODS: Proteomic profiles of 20 patient-derived glioblastoma xenografts (PDGX), established and genetically characterized at Duke's Preston Robert Tisch Brain Tumor Center, were obtained using Reverse Phase Protein Arrays (RPPA). The proteomic profiles of the parent tumors, obtained from Duke's brain tumor repository, were also obtained using RPPA. The RPPA analysis examined the expression of 128 proteins and phosphoproteins in each primary tumor and PDGX. We compared the expression levels of the 128 proteins in each PDGX/primary tumor pair by plotting the expression level on the y-axis and name of the protein/phosphoprotein on the x-axis. RESULTS: For each primary tumor and PDGX pair, the expression of all but 4 to 8 proteins matched. These data indicate that PDGX retain the protemic profile of the parent tumor. Since the proteomic profile provides information on activated growth pathways, these data can be used to develop an arsenal of signal transduction modulators effective in arresting PDGX growth. For example, 5 xenografts exhibited high phosphorylation of EGFR and these PDGX also showed significantly increased phsophorylation of five other proteins, including GSK3-β, HER2, MAPK, Rb, and Src. Thus, a decrease in phosphorylation of these five proteins can be used to monitor the effectiveness of EGFR blockade in silencing EGFR signaling. If the agents found to be effective in silencing EGFR signaling also inhibit xenograft growth, then these agents can be further tested in glioblastoma patients whose tumors have similar molecular features. CONCLUSIONS: A concordance between the proteomic/phosphoproteomic profiles of PDGX and their parent tumor makes the PDGX an excellent preclinical model for personalized drug development. Acknowledgements: This research is supported by a grant from the NIH (R21NS078642) and a grant from the Musella Foundation to MMK. SECONDARY CATEGORY: Tumor Biology.
Related Links	http://dx.doi.org/10.1093/neuonc/nou208.57
Starting Page	38
File Format	PDF
ISSN	15228517
e-ISSN	15235866
Journal	Neuro-Oncology
Issue Number	Suppl 3
Volume Number	16
Language	English
Publisher	Oxford University Press
Publisher Date	2014-07-01
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Cancer Research Oncology Clinical Neurology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Neurology (clinical) Oncology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Utility of Glioblastoma Patient-Derived Orthotopic Xenografts in Drug Discovery and Personalized Therapy

Proteomic profiling of patient-derived glioblastoma xenografts identifies a subset with activated EGFR: Implications for drug development

NT-29UPREGULATION OF BETA-CATENIN IN PATIENT-DERIVED GLIOBLASTOMA XENOGRAFTS EXPRESSING EGFRvIII

Real-time evaluation of glioblastoma growth in patient-specific zebrafish xenografts

The proteomic response in glioblastoma in young patients

Patient-derived breast tumor xenografts facilitating personalized cancer therapy

Patient-derived xenografts: a relevant preclinical model for drug development

An interleukin 13 receptor α 2–specific peptide homes to human Glioblastoma multiforme xenografts

Treatment with the PI3K inhibitor buparlisib (NVP-BKM120) suppresses the growth of established patient-derived GBM xenografts and prolongs survival in nude rats

PATIENT-DERIVED XENOGRAFTS MIRROR THE PROTEOMIC PROFILE OF HUMAN GLIOBLASTOMA: IMPLICATIONS FOR PERSONALIZED DRUG DEVELOPMENT

Similar Documents

Utility of Glioblastoma Patient-Derived Orthotopic Xenografts in Drug Discovery and Personalized Therapy

Proteomic profiling of patient-derived glioblastoma xenografts identifies a subset with activated EGFR: Implications for drug development

NT-29UPREGULATION OF BETA-CATENIN IN PATIENT-DERIVED GLIOBLASTOMA XENOGRAFTS EXPRESSING EGFRvIII

Real-time evaluation of glioblastoma growth in patient-specific zebrafish xenografts

The proteomic response in glioblastoma in young patients

Patient-derived breast tumor xenografts facilitating personalized cancer therapy

Patient-derived xenografts: a relevant preclinical model for drug development

An interleukin 13 receptor α 2–specific peptide homes to human Glioblastoma multiforme xenografts

Treatment with the PI3K inhibitor buparlisib (NVP-BKM120) suppresses the growth of established patient-derived GBM xenografts and prolongs survival in nude rats

PATIENT-DERIVED XENOGRAFTS MIRROR THE PROTEOMIC PROFILE OF HUMAN GLIOBLASTOMA: IMPLICATIONS FOR PERSONALIZED DRUG DEVELOPMENT