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Analyzing tyrosine kinase activity in head and neck cancer by functional kinomics: Identification of hyperactivated Src-family kinases as prognostic markers and potential targets

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Analyzing tyrosine kinase activity in head and neck cancer by functional kinomics: Identification of hyperactivated Src-family kinases as prognostic markers and potential targets. / Bußmann, Lara; Hoffer, Konstantin; von Bargen, Clara Marie; Droste, Conrad; Lange, Tobias; Kemmling, Julia; Schröder-Schwarz, Jennifer; Vu, Anh Thu; Akingunsade, Lara; Nollau, Peter; Rangarajan, Savithri; de Wijn, Rik; Oetting, Agnes; Müller, Christian; Böckelmann, Lukas Clemens; Zech, Henrike Barbara; Berger, Joanna Caroline; Möckelmann, Nikolaus; Busch, Chia-Jung; Böttcher, Arne; Gatzemeier, Fruzsina; Klinghammer, Konrad; Simnica, Donjete; Binder, Mascha; Struve, Nina; Rieckmann, Thorsten; Schumacher, Udo; Clauditz, Till Sebastian; Betz, Christian Stephan; Petersen, Cordula; Rothkamm, Kai; Münscher, Adrian; Kriegs, Malte.

In: INT J CANCER, Vol. 149, No. 5, 01.09.2021, p. 1166 - 1180.

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

Harvard

Bußmann, L, Hoffer, K, von Bargen, CM, Droste, C, Lange, T, Kemmling, J, Schröder-Schwarz, J, Vu, AT, Akingunsade, L, Nollau, P, Rangarajan, S, de Wijn, R, Oetting, A, Müller, C, Böckelmann, LC, Zech, HB, Berger, JC, Möckelmann, N, Busch, C-J, Böttcher, A, Gatzemeier, F, Klinghammer, K, Simnica, D, Binder, M, Struve, N, Rieckmann, T, Schumacher, U, Clauditz, TS, Betz, CS, Petersen, C, Rothkamm, K, Münscher, A & Kriegs, M 2021, 'Analyzing tyrosine kinase activity in head and neck cancer by functional kinomics: Identification of hyperactivated Src-family kinases as prognostic markers and potential targets', INT J CANCER, vol. 149, no. 5, pp. 1166 - 1180. https://doi.org/10.1002/ijc.33606

APA

Bußmann, L., Hoffer, K., von Bargen, C. M., Droste, C., Lange, T., Kemmling, J., Schröder-Schwarz, J., Vu, A. T., Akingunsade, L., Nollau, P., Rangarajan, S., de Wijn, R., Oetting, A., Müller, C., Böckelmann, L. C., Zech, H. B., Berger, J. C., Möckelmann, N., Busch, C-J., ... Kriegs, M. (2021). Analyzing tyrosine kinase activity in head and neck cancer by functional kinomics: Identification of hyperactivated Src-family kinases as prognostic markers and potential targets. INT J CANCER, 149(5), 1166 - 1180. https://doi.org/10.1002/ijc.33606

Vancouver

Bußmann L, Hoffer K, von Bargen CM, Droste C, Lange T, Kemmling J et al. Analyzing tyrosine kinase activity in head and neck cancer by functional kinomics: Identification of hyperactivated Src-family kinases as prognostic markers and potential targets. INT J CANCER. 2021 Sep 1;149(5):1166 - 1180. https://doi.org/10.1002/ijc.33606

Bibtex

@article{968b0d66bb474b37acd99d9da7f17cfa,
title = "Analyzing tyrosine kinase activity in head and neck cancer by functional kinomics: Identification of hyperactivated Src-family kinases as prognostic markers and potential targets",
abstract = "Signal transduction via protein kinases is of central importance in cancer biology and treatment. However, the clinical success of kinase inhibitors is often hampered by a lack of robust predictive biomarkers, which is also caused by the discrepancy between kinase expression and activity. Therefore, there is a need for functional tests to identify aberrantly activated kinases in individual patients. Here we present a systematic analysis of the tyrosine kinases in head and neck cancer using such a test-functional kinome profiling. We detected increased tyrosine kinase activity in tumors compared with their corresponding normal tissue. Moreover, we identified members of the family of Src kinases (Src family kinases [SFK]) to be aberrantly activated in the majority of the tumors, which was confirmed by additional methods. We could also show that SFK hyperphosphorylation is associated with poor prognosis, while inhibition of SFK impaired cell proliferation, especially in cells with hyperactive SFK. In summary, functional kinome profiling identified SFK to be frequently hyperactivated in head and neck squamous cell carcinoma. SFK may therefore be potential therapeutic targets. These results furthermore demonstrate how functional tests help to increase our understanding of cancer biology and support the expansion of precision oncology.",
keywords = "Aberrant kinase activity, Functional kinome profiling, Head and neck cancer, Src-family kinases, personalized targeted therapy",
author = "Lara Bu{\ss}mann and Konstantin Hoffer and {von Bargen}, {Clara Marie} and Conrad Droste and Tobias Lange and Julia Kemmling and Jennifer Schr{\"o}der-Schwarz and Vu, {Anh Thu} and Lara Akingunsade and Peter Nollau and Savithri Rangarajan and {de Wijn}, Rik and Agnes Oetting and Christian M{\"u}ller and B{\"o}ckelmann, {Lukas Clemens} and Zech, {Henrike Barbara} and Berger, {Joanna Caroline} and Nikolaus M{\"o}ckelmann and Chia-Jung Busch and Arne B{\"o}ttcher and Fruzsina Gatzemeier and Konrad Klinghammer and Donjete Simnica and Mascha Binder and Nina Struve and Thorsten Rieckmann and Udo Schumacher and Clauditz, {Till Sebastian} and Betz, {Christian Stephan} and Cordula Petersen and Kai Rothkamm and Adrian M{\"u}nscher and Malte Kriegs",
note = "Julia Kemmling: Anatomie und Exp. Morphologie; Lara Akingunsade: Strahlentherapie",
year = "2021",
month = sep,
day = "1",
doi = "10.1002/ijc.33606",
language = "English",
volume = "149",
pages = "1166 -- 1180",
journal = "INT J CANCER",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "5",

}

RIS

TY - JOUR

T1 - Analyzing tyrosine kinase activity in head and neck cancer by functional kinomics: Identification of hyperactivated Src-family kinases as prognostic markers and potential targets

AU - Bußmann, Lara

AU - Hoffer, Konstantin

AU - von Bargen, Clara Marie

AU - Droste, Conrad

AU - Lange, Tobias

AU - Kemmling, Julia

AU - Schröder-Schwarz, Jennifer

AU - Vu, Anh Thu

AU - Akingunsade, Lara

AU - Nollau, Peter

AU - Rangarajan, Savithri

AU - de Wijn, Rik

AU - Oetting, Agnes

AU - Müller, Christian

AU - Böckelmann, Lukas Clemens

AU - Zech, Henrike Barbara

AU - Berger, Joanna Caroline

AU - Möckelmann, Nikolaus

AU - Busch, Chia-Jung

AU - Böttcher, Arne

AU - Gatzemeier, Fruzsina

AU - Klinghammer, Konrad

AU - Simnica, Donjete

AU - Binder, Mascha

AU - Struve, Nina

AU - Rieckmann, Thorsten

AU - Schumacher, Udo

AU - Clauditz, Till Sebastian

AU - Betz, Christian Stephan

AU - Petersen, Cordula

AU - Rothkamm, Kai

AU - Münscher, Adrian

AU - Kriegs, Malte

N1 - Julia Kemmling: Anatomie und Exp. Morphologie; Lara Akingunsade: Strahlentherapie

PY - 2021/9/1

Y1 - 2021/9/1

N2 - Signal transduction via protein kinases is of central importance in cancer biology and treatment. However, the clinical success of kinase inhibitors is often hampered by a lack of robust predictive biomarkers, which is also caused by the discrepancy between kinase expression and activity. Therefore, there is a need for functional tests to identify aberrantly activated kinases in individual patients. Here we present a systematic analysis of the tyrosine kinases in head and neck cancer using such a test-functional kinome profiling. We detected increased tyrosine kinase activity in tumors compared with their corresponding normal tissue. Moreover, we identified members of the family of Src kinases (Src family kinases [SFK]) to be aberrantly activated in the majority of the tumors, which was confirmed by additional methods. We could also show that SFK hyperphosphorylation is associated with poor prognosis, while inhibition of SFK impaired cell proliferation, especially in cells with hyperactive SFK. In summary, functional kinome profiling identified SFK to be frequently hyperactivated in head and neck squamous cell carcinoma. SFK may therefore be potential therapeutic targets. These results furthermore demonstrate how functional tests help to increase our understanding of cancer biology and support the expansion of precision oncology.

AB - Signal transduction via protein kinases is of central importance in cancer biology and treatment. However, the clinical success of kinase inhibitors is often hampered by a lack of robust predictive biomarkers, which is also caused by the discrepancy between kinase expression and activity. Therefore, there is a need for functional tests to identify aberrantly activated kinases in individual patients. Here we present a systematic analysis of the tyrosine kinases in head and neck cancer using such a test-functional kinome profiling. We detected increased tyrosine kinase activity in tumors compared with their corresponding normal tissue. Moreover, we identified members of the family of Src kinases (Src family kinases [SFK]) to be aberrantly activated in the majority of the tumors, which was confirmed by additional methods. We could also show that SFK hyperphosphorylation is associated with poor prognosis, while inhibition of SFK impaired cell proliferation, especially in cells with hyperactive SFK. In summary, functional kinome profiling identified SFK to be frequently hyperactivated in head and neck squamous cell carcinoma. SFK may therefore be potential therapeutic targets. These results furthermore demonstrate how functional tests help to increase our understanding of cancer biology and support the expansion of precision oncology.

KW - Aberrant kinase activity

KW - Functional kinome profiling

KW - Head and neck cancer

KW - Src-family kinases

KW - personalized targeted therapy

UR - https://onlinelibrary.wiley.com/doi/10.1002/ijc.33961

U2 - 10.1002/ijc.33606

DO - 10.1002/ijc.33606

M3 - SCORING: Journal article

C2 - 33890294

VL - 149

SP - 1166

EP - 1180

JO - INT J CANCER

JF - INT J CANCER

SN - 0020-7136

IS - 5

ER -