A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer

Katrien Berns; Hugo M. Horlings; Bryan T. Hennessy; Mandy Madiredjo; E. Marielle Hijmans; Karin Beelen; Sabine C. Linn; Ana Maria Gonzalez-Angulo; Katherine Stemke-Hale; Michael Hauptmann; Roderick L. Beijersbergen; Gordon B. Mills; Marc J. van de Vijver; René Bernards

doi:https://doi.org/10.1016/j.ccr.2007.08.030

A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer

Katrien Berns, Hugo M. Horlings, Bryan T. Hennessy, Mandy Madiredjo, E. Marielle Hijmans, Karin Beelen, Sabine C. Linn, Ana Maria Gonzalez-Angulo, Katherine Stemke-Hale, Michael Hauptmann, Roderick L. Beijersbergen, Gordon B. Mills, Marc J. van de Vijver, René Bernards

Research output: Contribution to journal › Article › Academic › peer-review

1377 Citations (Scopus)

Abstract

A large-scale RNA interference screen to discover genes involved in trastuzumab resistance in breast cancer identified only PTEN as a modulator of drug sensitivity. Oncogenic mutants of PIK3CA (activator of the same pathway and frequently mutated in breast cancer) also conferred resistance to trastuzumab in cell culture. In a cohort of 55 breast cancer patients, activation of the PI3K pathway, as judged by the presence of oncogenic PIK3CA mutations or low PTEN expression, was associated with poor prognosis after trastuzumab therapy, and the combined analysis of PTEN and PIK3CA identified twice as many patients at increased risk for progression compared to PTEN alone. Thus, assessment of PI3K pathway activation may provide a biomarker to identify patients unlikely to respond to trastuzumab-based therapy

Original language	English
Pages (from-to)	395-402
Journal	Cancer cell
Volume	12
Issue number	4
DOIs	https://doi.org/10.1016/j.ccr.2007.08.030
Publication status	Published - 2007

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https://doi.org/10.1016/j.ccr.2007.08.030

Cite this

Berns, K., Horlings, H. M., Hennessy, B. T., Madiredjo, M., Hijmans, E. M., Beelen, K., Linn, S. C., Gonzalez-Angulo, A. M., Stemke-Hale, K., Hauptmann, M., Beijersbergen, R. L., Mills, G. B., van de Vijver, M. J., & Bernards, R. (2007). A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer cell, 12(4), 395-402. https://doi.org/10.1016/j.ccr.2007.08.030

@article{5fc5e0f44b5e4d6397069d454960dca4,

title = "A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer",

abstract = "A large-scale RNA interference screen to discover genes involved in trastuzumab resistance in breast cancer identified only PTEN as a modulator of drug sensitivity. Oncogenic mutants of PIK3CA (activator of the same pathway and frequently mutated in breast cancer) also conferred resistance to trastuzumab in cell culture. In a cohort of 55 breast cancer patients, activation of the PI3K pathway, as judged by the presence of oncogenic PIK3CA mutations or low PTEN expression, was associated with poor prognosis after trastuzumab therapy, and the combined analysis of PTEN and PIK3CA identified twice as many patients at increased risk for progression compared to PTEN alone. Thus, assessment of PI3K pathway activation may provide a biomarker to identify patients unlikely to respond to trastuzumab-based therapy",

author = "Katrien Berns and Horlings, {Hugo M.} and Hennessy, {Bryan T.} and Mandy Madiredjo and Hijmans, {E. Marielle} and Karin Beelen and Linn, {Sabine C.} and Gonzalez-Angulo, {Ana Maria} and Katherine Stemke-Hale and Michael Hauptmann and Beijersbergen, {Roderick L.} and Mills, {Gordon B.} and {van de Vijver}, {Marc J.} and Ren{\'e} Bernards",

year = "2007",

doi = "https://doi.org/10.1016/j.ccr.2007.08.030",

language = "English",

volume = "12",

pages = "395--402",

journal = "Cancer cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "4",

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Berns, K, Horlings, HM, Hennessy, BT, Madiredjo, M, Hijmans, EM, Beelen, K, Linn, SC, Gonzalez-Angulo, AM, Stemke-Hale, K, Hauptmann, M, Beijersbergen, RL, Mills, GB, van de Vijver, MJ & Bernards, R 2007, 'A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer', Cancer cell, vol. 12, no. 4, pp. 395-402. https://doi.org/10.1016/j.ccr.2007.08.030

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T1 - A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer

AU - Berns, Katrien

AU - Horlings, Hugo M.

AU - Hennessy, Bryan T.

AU - Madiredjo, Mandy

AU - Hijmans, E. Marielle

AU - Beelen, Karin

AU - Linn, Sabine C.

AU - Gonzalez-Angulo, Ana Maria

AU - Stemke-Hale, Katherine

AU - Hauptmann, Michael

AU - Beijersbergen, Roderick L.

AU - Mills, Gordon B.

AU - van de Vijver, Marc J.

AU - Bernards, René

PY - 2007

Y1 - 2007

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AB - A large-scale RNA interference screen to discover genes involved in trastuzumab resistance in breast cancer identified only PTEN as a modulator of drug sensitivity. Oncogenic mutants of PIK3CA (activator of the same pathway and frequently mutated in breast cancer) also conferred resistance to trastuzumab in cell culture. In a cohort of 55 breast cancer patients, activation of the PI3K pathway, as judged by the presence of oncogenic PIK3CA mutations or low PTEN expression, was associated with poor prognosis after trastuzumab therapy, and the combined analysis of PTEN and PIK3CA identified twice as many patients at increased risk for progression compared to PTEN alone. Thus, assessment of PI3K pathway activation may provide a biomarker to identify patients unlikely to respond to trastuzumab-based therapy

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DO - https://doi.org/10.1016/j.ccr.2007.08.030

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