Integrated mapping of pharmacokinetics and pharmacodynamics in a patient-derived xenograft model of glioblastoma

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Integrated mapping of pharmacokinetics and pharmacodynamics in a patient-derived xenograft model of glioblastoma. / Randall, Elizabeth C; Emdal, Kristina B; Laramy, Janice K; Kim, Minjee; Roos, Alison; Calligaris, David; Regan, Michael S; Gupta, Shiv K; Mladek, Ann C; Carlson, Brett L; Johnson, Aaron J; Lu, Fa-Ke; Xie, X Sunney; Joughin, Brian A; Reddy, Raven J; Peng, Sen; Abdelmoula, Walid M; Jackson, Pamela R; Kolluri, Aarti; Kellersberger, Katherine A; Agar, Jeffrey N; Lauffenburger, Douglas A; Swanson, Kristin R; Tran, Nhan L; Elmquist, William F; White, Forest M; Sarkaria, Jann N; Agar, Nathalie Y R.

In: Nature Communications, Vol. 9, No. 1, 21.11.2018, p. 4904.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Randall, EC, Emdal, KB, Laramy, JK, Kim, M, Roos, A, Calligaris, D, Regan, MS, Gupta, SK, Mladek, AC, Carlson, BL, Johnson, AJ, Lu, F-K, Xie, XS, Joughin, BA, Reddy, RJ, Peng, S, Abdelmoula, WM, Jackson, PR, Kolluri, A, Kellersberger, KA, Agar, JN, Lauffenburger, DA, Swanson, KR, Tran, NL, Elmquist, WF, White, FM, Sarkaria, JN & Agar, NYR 2018, 'Integrated mapping of pharmacokinetics and pharmacodynamics in a patient-derived xenograft model of glioblastoma', Nature Communications, vol. 9, no. 1, pp. 4904. https://doi.org/10.1038/s41467-018-07334-3

APA

Randall, E. C., Emdal, K. B., Laramy, J. K., Kim, M., Roos, A., Calligaris, D., Regan, M. S., Gupta, S. K., Mladek, A. C., Carlson, B. L., Johnson, A. J., Lu, F-K., Xie, X. S., Joughin, B. A., Reddy, R. J., Peng, S., Abdelmoula, W. M., Jackson, P. R., Kolluri, A., ... Agar, N. Y. R. (2018). Integrated mapping of pharmacokinetics and pharmacodynamics in a patient-derived xenograft model of glioblastoma. Nature Communications, 9(1), 4904. https://doi.org/10.1038/s41467-018-07334-3

Vancouver

Randall EC, Emdal KB, Laramy JK, Kim M, Roos A, Calligaris D et al. Integrated mapping of pharmacokinetics and pharmacodynamics in a patient-derived xenograft model of glioblastoma. Nature Communications. 2018 Nov 21;9(1):4904. https://doi.org/10.1038/s41467-018-07334-3

Author

Randall, Elizabeth C ; Emdal, Kristina B ; Laramy, Janice K ; Kim, Minjee ; Roos, Alison ; Calligaris, David ; Regan, Michael S ; Gupta, Shiv K ; Mladek, Ann C ; Carlson, Brett L ; Johnson, Aaron J ; Lu, Fa-Ke ; Xie, X Sunney ; Joughin, Brian A ; Reddy, Raven J ; Peng, Sen ; Abdelmoula, Walid M ; Jackson, Pamela R ; Kolluri, Aarti ; Kellersberger, Katherine A ; Agar, Jeffrey N ; Lauffenburger, Douglas A ; Swanson, Kristin R ; Tran, Nhan L ; Elmquist, William F ; White, Forest M ; Sarkaria, Jann N ; Agar, Nathalie Y R. / Integrated mapping of pharmacokinetics and pharmacodynamics in a patient-derived xenograft model of glioblastoma. In: Nature Communications. 2018 ; Vol. 9, No. 1. pp. 4904.

Bibtex

@article{25b80c2a17b340be9081bca8af4977ae,
title = "Integrated mapping of pharmacokinetics and pharmacodynamics in a patient-derived xenograft model of glioblastoma",
abstract = "Therapeutic options for the treatment of glioblastoma remain inadequate despite concerted research efforts in drug development. Therapeutic failure can result from poor permeability of the blood-brain barrier, heterogeneous drug distribution, and development of resistance. Elucidation of relationships among such parameters could enable the development of predictive models of drug response in patients and inform drug development. Complementary analyses were applied to a glioblastoma patient-derived xenograft model in order to quantitatively map distribution and resulting cellular response to the EGFR inhibitor erlotinib. Mass spectrometry images of erlotinib were registered to histology and magnetic resonance images in order to correlate drug distribution with tumor characteristics. Phosphoproteomics and immunohistochemistry were used to assess protein signaling in response to drug, and integrated with transcriptional response using mRNA sequencing. This comprehensive dataset provides simultaneous insight into pharmacokinetics and pharmacodynamics and indicates that erlotinib delivery to intracranial tumors is insufficient to inhibit EGFR tyrosine kinase signaling.",
author = "Randall, {Elizabeth C} and Emdal, {Kristina B} and Laramy, {Janice K} and Minjee Kim and Alison Roos and David Calligaris and Regan, {Michael S} and Gupta, {Shiv K} and Mladek, {Ann C} and Carlson, {Brett L} and Johnson, {Aaron J} and Fa-Ke Lu and Xie, {X Sunney} and Joughin, {Brian A} and Reddy, {Raven J} and Sen Peng and Abdelmoula, {Walid M} and Jackson, {Pamela R} and Aarti Kolluri and Kellersberger, {Katherine A} and Agar, {Jeffrey N} and Lauffenburger, {Douglas A} and Swanson, {Kristin R} and Tran, {Nhan L} and Elmquist, {William F} and White, {Forest M} and Sarkaria, {Jann N} and Agar, {Nathalie Y R}",
year = "2018",
month = nov,
day = "21",
doi = "10.1038/s41467-018-07334-3",
language = "English",
volume = "9",
pages = "4904",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Integrated mapping of pharmacokinetics and pharmacodynamics in a patient-derived xenograft model of glioblastoma

AU - Randall, Elizabeth C

AU - Emdal, Kristina B

AU - Laramy, Janice K

AU - Kim, Minjee

AU - Roos, Alison

AU - Calligaris, David

AU - Regan, Michael S

AU - Gupta, Shiv K

AU - Mladek, Ann C

AU - Carlson, Brett L

AU - Johnson, Aaron J

AU - Lu, Fa-Ke

AU - Xie, X Sunney

AU - Joughin, Brian A

AU - Reddy, Raven J

AU - Peng, Sen

AU - Abdelmoula, Walid M

AU - Jackson, Pamela R

AU - Kolluri, Aarti

AU - Kellersberger, Katherine A

AU - Agar, Jeffrey N

AU - Lauffenburger, Douglas A

AU - Swanson, Kristin R

AU - Tran, Nhan L

AU - Elmquist, William F

AU - White, Forest M

AU - Sarkaria, Jann N

AU - Agar, Nathalie Y R

PY - 2018/11/21

Y1 - 2018/11/21

N2 - Therapeutic options for the treatment of glioblastoma remain inadequate despite concerted research efforts in drug development. Therapeutic failure can result from poor permeability of the blood-brain barrier, heterogeneous drug distribution, and development of resistance. Elucidation of relationships among such parameters could enable the development of predictive models of drug response in patients and inform drug development. Complementary analyses were applied to a glioblastoma patient-derived xenograft model in order to quantitatively map distribution and resulting cellular response to the EGFR inhibitor erlotinib. Mass spectrometry images of erlotinib were registered to histology and magnetic resonance images in order to correlate drug distribution with tumor characteristics. Phosphoproteomics and immunohistochemistry were used to assess protein signaling in response to drug, and integrated with transcriptional response using mRNA sequencing. This comprehensive dataset provides simultaneous insight into pharmacokinetics and pharmacodynamics and indicates that erlotinib delivery to intracranial tumors is insufficient to inhibit EGFR tyrosine kinase signaling.

AB - Therapeutic options for the treatment of glioblastoma remain inadequate despite concerted research efforts in drug development. Therapeutic failure can result from poor permeability of the blood-brain barrier, heterogeneous drug distribution, and development of resistance. Elucidation of relationships among such parameters could enable the development of predictive models of drug response in patients and inform drug development. Complementary analyses were applied to a glioblastoma patient-derived xenograft model in order to quantitatively map distribution and resulting cellular response to the EGFR inhibitor erlotinib. Mass spectrometry images of erlotinib were registered to histology and magnetic resonance images in order to correlate drug distribution with tumor characteristics. Phosphoproteomics and immunohistochemistry were used to assess protein signaling in response to drug, and integrated with transcriptional response using mRNA sequencing. This comprehensive dataset provides simultaneous insight into pharmacokinetics and pharmacodynamics and indicates that erlotinib delivery to intracranial tumors is insufficient to inhibit EGFR tyrosine kinase signaling.

U2 - 10.1038/s41467-018-07334-3

DO - 10.1038/s41467-018-07334-3

M3 - Journal article

C2 - 30464169

VL - 9

SP - 4904

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

ER -

ID: 209323322