Establishing a Preclinical Multidisciplinary Board for Brain Tumors

Publication Date:
2018-04-04
Publisher:
The American Association for Cancer Research (AACR)
Print ISSN:
1078-0432
Electronic ISSN:
1557-3265
Topics:
Medicine
Published by:
http://www.aacr.org/
_version_ 1836398875487764480
autor Nimmervoll, B. V., Boulos, N., Bianski, B., Dapper, J., De; Cuypere, M., Shelat, A., Terranova, S., Terhune, H. E., Gajjar, A., Patel, Y. T., Freeman, B. B., Onar-Thomas, A., Stewart, C. F., Roussel, M. F., Guy, R. K., Merchant, T. E., Calabrese, C., Wright, K. D., Gilbertson, R. J.
beschreibung Purpose: Curing all children with brain tumors will require an understanding of how each subtype responds to conventional treatments and how best to combine existing and novel therapies. It is extremely challenging to acquire this knowledge in the clinic alone, especially among patients with rare tumors. Therefore, we developed a preclinical brain tumor platform to test combinations of conventional and novel therapies in a manner that closely recapitulates clinic trials. Experimental Design: A multidisciplinary team was established to design and conduct neurosurgical, fractionated radiotherapy and chemotherapy studies, alone or in combination, in accurate mouse models of supratentorial ependymoma (SEP) subtypes and choroid plexus carcinoma (CPC). Extensive drug repurposing screens, pharmacokinetic, pharmacodynamic, and efficacy studies were used to triage active compounds for combination preclinical trials with "standard-of-care" surgery and radiotherapy. Results: Mouse models displayed distinct patterns of response to surgery, irradiation, and chemotherapy that varied with tumor subtype. Repurposing screens identified 3-hour infusions of gemcitabine as a relatively nontoxic and efficacious treatment of SEP and CPC. Combination neurosurgery, fractionated irradiation, and gemcitabine proved significantly more effective than surgery and irradiation alone, curing one half of all animals with aggressive forms of SEP. Conclusions: We report a comprehensive preclinical trial platform to assess the therapeutic activity of conventional and novel treatments among rare brain tumor subtypes. It also enables the development of complex, combination treatment regimens that should deliver optimal trial designs for clinical testing. Postirradiation gemcitabine infusion should be tested as new treatments of SEP and CPC. Clin Cancer Res; 24(7); 1654–66. ©2018 AACR .
citation_standardnr 6224608
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feed_publisher The American Association for Cancer Research (AACR)
feed_publisher_url http://www.aacr.org/
insertion_date 2018-04-04
journaleissn 1557-3265
journalissn 1078-0432
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Association for Cancer Research (AACR)
quelle Clinical Cancer Research
relation http://clincancerres.aacrjournals.org/cgi/content/short/24/7/1654?rss=1
search_space articles
shingle_author_1 Nimmervoll, B. V., Boulos, N., Bianski, B., Dapper, J., De; Cuypere, M., Shelat, A., Terranova, S., Terhune, H. E., Gajjar, A., Patel, Y. T., Freeman, B. B., Onar-Thomas, A., Stewart, C. F., Roussel, M. F., Guy, R. K., Merchant, T. E., Calabrese, C., Wright, K. D., Gilbertson, R. J.
shingle_author_2 Nimmervoll, B. V., Boulos, N., Bianski, B., Dapper, J., De; Cuypere, M., Shelat, A., Terranova, S., Terhune, H. E., Gajjar, A., Patel, Y. T., Freeman, B. B., Onar-Thomas, A., Stewart, C. F., Roussel, M. F., Guy, R. K., Merchant, T. E., Calabrese, C., Wright, K. D., Gilbertson, R. J.
shingle_author_3 Nimmervoll, B. V., Boulos, N., Bianski, B., Dapper, J., De; Cuypere, M., Shelat, A., Terranova, S., Terhune, H. E., Gajjar, A., Patel, Y. T., Freeman, B. B., Onar-Thomas, A., Stewart, C. F., Roussel, M. F., Guy, R. K., Merchant, T. E., Calabrese, C., Wright, K. D., Gilbertson, R. J.
shingle_author_4 Nimmervoll, B. V., Boulos, N., Bianski, B., Dapper, J., De; Cuypere, M., Shelat, A., Terranova, S., Terhune, H. E., Gajjar, A., Patel, Y. T., Freeman, B. B., Onar-Thomas, A., Stewart, C. F., Roussel, M. F., Guy, R. K., Merchant, T. E., Calabrese, C., Wright, K. D., Gilbertson, R. J.
shingle_catch_all_1 Establishing a Preclinical Multidisciplinary Board for Brain Tumors
Purpose: Curing all children with brain tumors will require an understanding of how each subtype responds to conventional treatments and how best to combine existing and novel therapies. It is extremely challenging to acquire this knowledge in the clinic alone, especially among patients with rare tumors. Therefore, we developed a preclinical brain tumor platform to test combinations of conventional and novel therapies in a manner that closely recapitulates clinic trials. Experimental Design: A multidisciplinary team was established to design and conduct neurosurgical, fractionated radiotherapy and chemotherapy studies, alone or in combination, in accurate mouse models of supratentorial ependymoma (SEP) subtypes and choroid plexus carcinoma (CPC). Extensive drug repurposing screens, pharmacokinetic, pharmacodynamic, and efficacy studies were used to triage active compounds for combination preclinical trials with "standard-of-care" surgery and radiotherapy. Results: Mouse models displayed distinct patterns of response to surgery, irradiation, and chemotherapy that varied with tumor subtype. Repurposing screens identified 3-hour infusions of gemcitabine as a relatively nontoxic and efficacious treatment of SEP and CPC. Combination neurosurgery, fractionated irradiation, and gemcitabine proved significantly more effective than surgery and irradiation alone, curing one half of all animals with aggressive forms of SEP. Conclusions: We report a comprehensive preclinical trial platform to assess the therapeutic activity of conventional and novel treatments among rare brain tumor subtypes. It also enables the development of complex, combination treatment regimens that should deliver optimal trial designs for clinical testing. Postirradiation gemcitabine infusion should be tested as new treatments of SEP and CPC. Clin Cancer Res; 24(7); 1654–66. ©2018 AACR .
Nimmervoll, B. V., Boulos, N., Bianski, B., Dapper, J., De; Cuypere, M., Shelat, A., Terranova, S., Terhune, H. E., Gajjar, A., Patel, Y. T., Freeman, B. B., Onar-Thomas, A., Stewart, C. F., Roussel, M. F., Guy, R. K., Merchant, T. E., Calabrese, C., Wright, K. D., Gilbertson, R. J.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_2 Establishing a Preclinical Multidisciplinary Board for Brain Tumors
Purpose: Curing all children with brain tumors will require an understanding of how each subtype responds to conventional treatments and how best to combine existing and novel therapies. It is extremely challenging to acquire this knowledge in the clinic alone, especially among patients with rare tumors. Therefore, we developed a preclinical brain tumor platform to test combinations of conventional and novel therapies in a manner that closely recapitulates clinic trials. Experimental Design: A multidisciplinary team was established to design and conduct neurosurgical, fractionated radiotherapy and chemotherapy studies, alone or in combination, in accurate mouse models of supratentorial ependymoma (SEP) subtypes and choroid plexus carcinoma (CPC). Extensive drug repurposing screens, pharmacokinetic, pharmacodynamic, and efficacy studies were used to triage active compounds for combination preclinical trials with "standard-of-care" surgery and radiotherapy. Results: Mouse models displayed distinct patterns of response to surgery, irradiation, and chemotherapy that varied with tumor subtype. Repurposing screens identified 3-hour infusions of gemcitabine as a relatively nontoxic and efficacious treatment of SEP and CPC. Combination neurosurgery, fractionated irradiation, and gemcitabine proved significantly more effective than surgery and irradiation alone, curing one half of all animals with aggressive forms of SEP. Conclusions: We report a comprehensive preclinical trial platform to assess the therapeutic activity of conventional and novel treatments among rare brain tumor subtypes. It also enables the development of complex, combination treatment regimens that should deliver optimal trial designs for clinical testing. Postirradiation gemcitabine infusion should be tested as new treatments of SEP and CPC. Clin Cancer Res; 24(7); 1654–66. ©2018 AACR .
Nimmervoll, B. V., Boulos, N., Bianski, B., Dapper, J., De; Cuypere, M., Shelat, A., Terranova, S., Terhune, H. E., Gajjar, A., Patel, Y. T., Freeman, B. B., Onar-Thomas, A., Stewart, C. F., Roussel, M. F., Guy, R. K., Merchant, T. E., Calabrese, C., Wright, K. D., Gilbertson, R. J.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_3 Establishing a Preclinical Multidisciplinary Board for Brain Tumors
Purpose: Curing all children with brain tumors will require an understanding of how each subtype responds to conventional treatments and how best to combine existing and novel therapies. It is extremely challenging to acquire this knowledge in the clinic alone, especially among patients with rare tumors. Therefore, we developed a preclinical brain tumor platform to test combinations of conventional and novel therapies in a manner that closely recapitulates clinic trials. Experimental Design: A multidisciplinary team was established to design and conduct neurosurgical, fractionated radiotherapy and chemotherapy studies, alone or in combination, in accurate mouse models of supratentorial ependymoma (SEP) subtypes and choroid plexus carcinoma (CPC). Extensive drug repurposing screens, pharmacokinetic, pharmacodynamic, and efficacy studies were used to triage active compounds for combination preclinical trials with "standard-of-care" surgery and radiotherapy. Results: Mouse models displayed distinct patterns of response to surgery, irradiation, and chemotherapy that varied with tumor subtype. Repurposing screens identified 3-hour infusions of gemcitabine as a relatively nontoxic and efficacious treatment of SEP and CPC. Combination neurosurgery, fractionated irradiation, and gemcitabine proved significantly more effective than surgery and irradiation alone, curing one half of all animals with aggressive forms of SEP. Conclusions: We report a comprehensive preclinical trial platform to assess the therapeutic activity of conventional and novel treatments among rare brain tumor subtypes. It also enables the development of complex, combination treatment regimens that should deliver optimal trial designs for clinical testing. Postirradiation gemcitabine infusion should be tested as new treatments of SEP and CPC. Clin Cancer Res; 24(7); 1654–66. ©2018 AACR .
Nimmervoll, B. V., Boulos, N., Bianski, B., Dapper, J., De; Cuypere, M., Shelat, A., Terranova, S., Terhune, H. E., Gajjar, A., Patel, Y. T., Freeman, B. B., Onar-Thomas, A., Stewart, C. F., Roussel, M. F., Guy, R. K., Merchant, T. E., Calabrese, C., Wright, K. D., Gilbertson, R. J.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_4 Establishing a Preclinical Multidisciplinary Board for Brain Tumors
Purpose: Curing all children with brain tumors will require an understanding of how each subtype responds to conventional treatments and how best to combine existing and novel therapies. It is extremely challenging to acquire this knowledge in the clinic alone, especially among patients with rare tumors. Therefore, we developed a preclinical brain tumor platform to test combinations of conventional and novel therapies in a manner that closely recapitulates clinic trials. Experimental Design: A multidisciplinary team was established to design and conduct neurosurgical, fractionated radiotherapy and chemotherapy studies, alone or in combination, in accurate mouse models of supratentorial ependymoma (SEP) subtypes and choroid plexus carcinoma (CPC). Extensive drug repurposing screens, pharmacokinetic, pharmacodynamic, and efficacy studies were used to triage active compounds for combination preclinical trials with "standard-of-care" surgery and radiotherapy. Results: Mouse models displayed distinct patterns of response to surgery, irradiation, and chemotherapy that varied with tumor subtype. Repurposing screens identified 3-hour infusions of gemcitabine as a relatively nontoxic and efficacious treatment of SEP and CPC. Combination neurosurgery, fractionated irradiation, and gemcitabine proved significantly more effective than surgery and irradiation alone, curing one half of all animals with aggressive forms of SEP. Conclusions: We report a comprehensive preclinical trial platform to assess the therapeutic activity of conventional and novel treatments among rare brain tumor subtypes. It also enables the development of complex, combination treatment regimens that should deliver optimal trial designs for clinical testing. Postirradiation gemcitabine infusion should be tested as new treatments of SEP and CPC. Clin Cancer Res; 24(7); 1654–66. ©2018 AACR .
Nimmervoll, B. V., Boulos, N., Bianski, B., Dapper, J., De; Cuypere, M., Shelat, A., Terranova, S., Terhune, H. E., Gajjar, A., Patel, Y. T., Freeman, B. B., Onar-Thomas, A., Stewart, C. F., Roussel, M. F., Guy, R. K., Merchant, T. E., Calabrese, C., Wright, K. D., Gilbertson, R. J.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_title_1 Establishing a Preclinical Multidisciplinary Board for Brain Tumors
shingle_title_2 Establishing a Preclinical Multidisciplinary Board for Brain Tumors
shingle_title_3 Establishing a Preclinical Multidisciplinary Board for Brain Tumors
shingle_title_4 Establishing a Preclinical Multidisciplinary Board for Brain Tumors
timestamp 2025-06-30T23:34:01.985Z
titel Establishing a Preclinical Multidisciplinary Board for Brain Tumors
titel_suche Establishing a Preclinical Multidisciplinary Board for Brain Tumors
topic WW-YZ
uid ipn_articles_6224608