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Testing of SNS-032 in a Panel of Human Neuroblastoma Cell Lines with Acquired Resistance to a Broad Range of Drugs

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Testing of SNS-032 in a Panel of Human Neuroblastoma Cell Lines with Acquired Resistance to a Broad Range of Drugs. / Löschmann, Nadine; Michaelis, Martin; Rothweiler, Florian; Zehner, Richard; Cinatl, Jaroslav; Voges, Yvonne; Sharifi, Mohsen; Riecken, Kristoffer; Meyer, Jochen; von Deimling, Andreas; Fichtner, Iduna; Ghafourian, Taravat; Westermann, Frank; Cinatl, Jindrich.

In: TRANSL ONCOL, Vol. 6, No. 6, 01.12.2013, p. 685-96.

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

Harvard

Löschmann, N, Michaelis, M, Rothweiler, F, Zehner, R, Cinatl, J, Voges, Y, Sharifi, M, Riecken, K, Meyer, J, von Deimling, A, Fichtner, I, Ghafourian, T, Westermann, F & Cinatl, J 2013, 'Testing of SNS-032 in a Panel of Human Neuroblastoma Cell Lines with Acquired Resistance to a Broad Range of Drugs', TRANSL ONCOL, vol. 6, no. 6, pp. 685-96.

APA

Löschmann, N., Michaelis, M., Rothweiler, F., Zehner, R., Cinatl, J., Voges, Y., Sharifi, M., Riecken, K., Meyer, J., von Deimling, A., Fichtner, I., Ghafourian, T., Westermann, F., & Cinatl, J. (2013). Testing of SNS-032 in a Panel of Human Neuroblastoma Cell Lines with Acquired Resistance to a Broad Range of Drugs. TRANSL ONCOL, 6(6), 685-96.

Vancouver

Löschmann N, Michaelis M, Rothweiler F, Zehner R, Cinatl J, Voges Y et al. Testing of SNS-032 in a Panel of Human Neuroblastoma Cell Lines with Acquired Resistance to a Broad Range of Drugs. TRANSL ONCOL. 2013 Dec 1;6(6):685-96.

Bibtex

@article{22ec467b0d784d6dab0ae44ff8a2151b,
title = "Testing of SNS-032 in a Panel of Human Neuroblastoma Cell Lines with Acquired Resistance to a Broad Range of Drugs",
abstract = "Novel treatment options are needed for the successful therapy of patients with high-risk neuroblastoma. Here, we investigated the cyclin-dependent kinase (CDK) inhibitor SNS-032 in a panel of 109 neuroblastoma cell lines consisting of 19 parental cell lines and 90 sublines with acquired resistance to 14 different anticancer drugs. Seventy-three percent of the investigated neuroblastoma cell lines and all four investigated primary tumor samples displayed concentrations that reduce cell viability by 50% in the range of the therapeutic plasma levels reported for SNS-032 (<754 nM). Sixty-two percent of the cell lines and two of the primary samples displayed concentrations that reduce cell viability by 90% in this concentration range. SNS-032 also impaired the growth of the multidrug-resistant cisplatin-adapted UKF-NB-3 subline UKF-NB-3(r)CDDP(1000) in mice. ABCB1 expression (but not ABCG2 expression) conferred resistance to SNS-032. The antineuroblastoma effects of SNS-032 did not depend on functional p53. The antineuroblastoma mechanism of SNS-032 included CDK7 and CDK9 inhibition-mediated suppression of RNA synthesis and subsequent depletion of antiapoptotic proteins with a fast turnover rate including X-linked inhibitor of apoptosis (XIAP), myeloid cell leukemia sequence 1 (Mcl-1), baculoviral IAP repeat containing 2 (BIRC2; cIAP-1), and survivin. In conclusion, CDK7 and CDK9 represent promising drug targets and SNS-032 represents a potential treatment option for neuroblastoma including therapy-refractory cases.",
author = "Nadine L{\"o}schmann and Martin Michaelis and Florian Rothweiler and Richard Zehner and Jaroslav Cinatl and Yvonne Voges and Mohsen Sharifi and Kristoffer Riecken and Jochen Meyer and {von Deimling}, Andreas and Iduna Fichtner and Taravat Ghafourian and Frank Westermann and Jindrich Cinatl",
year = "2013",
month = dec,
day = "1",
language = "English",
volume = "6",
pages = "685--96",
journal = "TRANSL ONCOL",
issn = "1936-5233",
publisher = "Neoplasia Press",
number = "6",

}

RIS

TY - JOUR

T1 - Testing of SNS-032 in a Panel of Human Neuroblastoma Cell Lines with Acquired Resistance to a Broad Range of Drugs

AU - Löschmann, Nadine

AU - Michaelis, Martin

AU - Rothweiler, Florian

AU - Zehner, Richard

AU - Cinatl, Jaroslav

AU - Voges, Yvonne

AU - Sharifi, Mohsen

AU - Riecken, Kristoffer

AU - Meyer, Jochen

AU - von Deimling, Andreas

AU - Fichtner, Iduna

AU - Ghafourian, Taravat

AU - Westermann, Frank

AU - Cinatl, Jindrich

PY - 2013/12/1

Y1 - 2013/12/1

N2 - Novel treatment options are needed for the successful therapy of patients with high-risk neuroblastoma. Here, we investigated the cyclin-dependent kinase (CDK) inhibitor SNS-032 in a panel of 109 neuroblastoma cell lines consisting of 19 parental cell lines and 90 sublines with acquired resistance to 14 different anticancer drugs. Seventy-three percent of the investigated neuroblastoma cell lines and all four investigated primary tumor samples displayed concentrations that reduce cell viability by 50% in the range of the therapeutic plasma levels reported for SNS-032 (<754 nM). Sixty-two percent of the cell lines and two of the primary samples displayed concentrations that reduce cell viability by 90% in this concentration range. SNS-032 also impaired the growth of the multidrug-resistant cisplatin-adapted UKF-NB-3 subline UKF-NB-3(r)CDDP(1000) in mice. ABCB1 expression (but not ABCG2 expression) conferred resistance to SNS-032. The antineuroblastoma effects of SNS-032 did not depend on functional p53. The antineuroblastoma mechanism of SNS-032 included CDK7 and CDK9 inhibition-mediated suppression of RNA synthesis and subsequent depletion of antiapoptotic proteins with a fast turnover rate including X-linked inhibitor of apoptosis (XIAP), myeloid cell leukemia sequence 1 (Mcl-1), baculoviral IAP repeat containing 2 (BIRC2; cIAP-1), and survivin. In conclusion, CDK7 and CDK9 represent promising drug targets and SNS-032 represents a potential treatment option for neuroblastoma including therapy-refractory cases.

AB - Novel treatment options are needed for the successful therapy of patients with high-risk neuroblastoma. Here, we investigated the cyclin-dependent kinase (CDK) inhibitor SNS-032 in a panel of 109 neuroblastoma cell lines consisting of 19 parental cell lines and 90 sublines with acquired resistance to 14 different anticancer drugs. Seventy-three percent of the investigated neuroblastoma cell lines and all four investigated primary tumor samples displayed concentrations that reduce cell viability by 50% in the range of the therapeutic plasma levels reported for SNS-032 (<754 nM). Sixty-two percent of the cell lines and two of the primary samples displayed concentrations that reduce cell viability by 90% in this concentration range. SNS-032 also impaired the growth of the multidrug-resistant cisplatin-adapted UKF-NB-3 subline UKF-NB-3(r)CDDP(1000) in mice. ABCB1 expression (but not ABCG2 expression) conferred resistance to SNS-032. The antineuroblastoma effects of SNS-032 did not depend on functional p53. The antineuroblastoma mechanism of SNS-032 included CDK7 and CDK9 inhibition-mediated suppression of RNA synthesis and subsequent depletion of antiapoptotic proteins with a fast turnover rate including X-linked inhibitor of apoptosis (XIAP), myeloid cell leukemia sequence 1 (Mcl-1), baculoviral IAP repeat containing 2 (BIRC2; cIAP-1), and survivin. In conclusion, CDK7 and CDK9 represent promising drug targets and SNS-032 represents a potential treatment option for neuroblastoma including therapy-refractory cases.

M3 - SCORING: Journal article

C2 - 24466371

VL - 6

SP - 685

EP - 696

JO - TRANSL ONCOL

JF - TRANSL ONCOL

SN - 1936-5233

IS - 6

ER -