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RSK3/4 mediate resistance to PI3K pathway inhibitors in breast cancer
Violeta Serra,1 Pieter J.A. Eichhorn,2 Celina García-García,1 Yasir H. Ibrahim,1 Ludmila Prudkin,3 Gertrudis Sánchez,3 Olga Rodríguez,1 Pilar Antón,1 Josep-Lluís Parra,4 Sara Marlow,5 Maurizio Scaltriti,6 José Pérez-Garcia,7 Aleix Prat,8 Joaquín Arribas,4,9 William C. Hahn,9,10 So Young Kim,11 and José Baselga1,6
1Experimental Therapeutics, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 2Cancer Science Institute of Singapore, National University of Singapore, Singapore. 3Molecular Pathology and 4Growth Factors Groups, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 5Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA. 6Human Oncology and Pathogenesis Program and Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 7Breast Cancer and Melanoma Group and 8Translational Genomics Unit, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 9Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. 10Center for Cancer Genome Discovery, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. 11Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. 12Department of Molecular Genetics and Microbiology, Duke RNAi Screening Facility, Duke University Medical Center, Durham, North Carolina, USA.
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1Experimental Therapeutics, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 2Cancer Science Institute of Singapore, National University of Singapore, Singapore. 3Molecular Pathology and 4Growth Factors Groups, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 5Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA. 6Human Oncology and Pathogenesis Program and Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 7Breast Cancer and Melanoma Group and 8Translational Genomics Unit, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 9Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. 10Center for Cancer Genome Discovery, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. 11Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. 12Department of Molecular Genetics and Microbiology, Duke RNAi Screening Facility, Duke University Medical Center, Durham, North Carolina, USA.
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1Experimental Therapeutics, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 2Cancer Science Institute of Singapore, National University of Singapore, Singapore. 3Molecular Pathology and 4Growth Factors Groups, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 5Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA. 6Human Oncology and Pathogenesis Program and Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 7Breast Cancer and Melanoma Group and 8Translational Genomics Unit, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 9Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. 10Center for Cancer Genome Discovery, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. 11Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. 12Department of Molecular Genetics and Microbiology, Duke RNAi Screening Facility, Duke University Medical Center, Durham, North Carolina, USA.
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1Experimental Therapeutics, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 2Cancer Science Institute of Singapore, National University of Singapore, Singapore. 3Molecular Pathology and 4Growth Factors Groups, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 5Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA. 6Human Oncology and Pathogenesis Program and Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 7Breast Cancer and Melanoma Group and 8Translational Genomics Unit, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 9Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. 10Center for Cancer Genome Discovery, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. 11Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. 12Department of Molecular Genetics and Microbiology, Duke RNAi Screening Facility, Duke University Medical Center, Durham, North Carolina, USA.
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1Experimental Therapeutics, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 2Cancer Science Institute of Singapore, National University of Singapore, Singapore. 3Molecular Pathology and 4Growth Factors Groups, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 5Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA. 6Human Oncology and Pathogenesis Program and Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 7Breast Cancer and Melanoma Group and 8Translational Genomics Unit, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 9Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. 10Center for Cancer Genome Discovery, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. 11Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. 12Department of Molecular Genetics and Microbiology, Duke RNAi Screening Facility, Duke University Medical Center, Durham, North Carolina, USA.
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1Experimental Therapeutics, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 2Cancer Science Institute of Singapore, National University of Singapore, Singapore. 3Molecular Pathology and 4Growth Factors Groups, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 5Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA. 6Human Oncology and Pathogenesis Program and Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 7Breast Cancer and Melanoma Group and 8Translational Genomics Unit, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 9Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. 10Center for Cancer Genome Discovery, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. 11Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. 12Department of Molecular Genetics and Microbiology, Duke RNAi Screening Facility, Duke University Medical Center, Durham, North Carolina, USA.
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1Experimental Therapeutics, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 2Cancer Science Institute of Singapore, National University of Singapore, Singapore. 3Molecular Pathology and 4Growth Factors Groups, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 5Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA. 6Human Oncology and Pathogenesis Program and Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 7Breast Cancer and Melanoma Group and 8Translational Genomics Unit, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 9Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. 10Center for Cancer Genome Discovery, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. 11Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. 12Department of Molecular Genetics and Microbiology, Duke RNAi Screening Facility, Duke University Medical Center, Durham, North Carolina, USA.
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1Experimental Therapeutics, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 2Cancer Science Institute of Singapore, National University of Singapore, Singapore. 3Molecular Pathology and 4Growth Factors Groups, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 5Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA. 6Human Oncology and Pathogenesis Program and Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 7Breast Cancer and Melanoma Group and 8Translational Genomics Unit, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 9Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. 10Center for Cancer Genome Discovery, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. 11Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. 12Department of Molecular Genetics and Microbiology, Duke RNAi Screening Facility, Duke University Medical Center, Durham, North Carolina, USA.
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1Experimental Therapeutics, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 2Cancer Science Institute of Singapore, National University of Singapore, Singapore. 3Molecular Pathology and 4Growth Factors Groups, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 5Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA. 6Human Oncology and Pathogenesis Program and Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 7Breast Cancer and Melanoma Group and 8Translational Genomics Unit, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 9Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. 10Center for Cancer Genome Discovery, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. 11Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. 12Department of Molecular Genetics and Microbiology, Duke RNAi Screening Facility, Duke University Medical Center, Durham, North Carolina, USA.
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1Experimental Therapeutics, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 2Cancer Science Institute of Singapore, National University of Singapore, Singapore. 3Molecular Pathology and 4Growth Factors Groups, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 5Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA. 6Human Oncology and Pathogenesis Program and Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 7Breast Cancer and Melanoma Group and 8Translational Genomics Unit, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 9Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. 10Center for Cancer Genome Discovery, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. 11Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. 12Department of Molecular Genetics and Microbiology, Duke RNAi Screening Facility, Duke University Medical Center, Durham, North Carolina, USA.
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1Experimental Therapeutics, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 2Cancer Science Institute of Singapore, National University of Singapore, Singapore. 3Molecular Pathology and 4Growth Factors Groups, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 5Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA. 6Human Oncology and Pathogenesis Program and Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 7Breast Cancer and Melanoma Group and 8Translational Genomics Unit, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 9Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. 10Center for Cancer Genome Discovery, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. 11Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. 12Department of Molecular Genetics and Microbiology, Duke RNAi Screening Facility, Duke University Medical Center, Durham, North Carolina, USA.
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1Experimental Therapeutics, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 2Cancer Science Institute of Singapore, National University of Singapore, Singapore. 3Molecular Pathology and 4Growth Factors Groups, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 5Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA. 6Human Oncology and Pathogenesis Program and Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 7Breast Cancer and Melanoma Group and 8Translational Genomics Unit, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 9Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. 10Center for Cancer Genome Discovery, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. 11Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. 12Department of Molecular Genetics and Microbiology, Duke RNAi Screening Facility, Duke University Medical Center, Durham, North Carolina, USA.
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1Experimental Therapeutics, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 2Cancer Science Institute of Singapore, National University of Singapore, Singapore. 3Molecular Pathology and 4Growth Factors Groups, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 5Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA. 6Human Oncology and Pathogenesis Program and Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 7Breast Cancer and Melanoma Group and 8Translational Genomics Unit, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 9Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. 10Center for Cancer Genome Discovery, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. 11Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. 12Department of Molecular Genetics and Microbiology, Duke RNAi Screening Facility, Duke University Medical Center, Durham, North Carolina, USA.
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1Experimental Therapeutics, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 2Cancer Science Institute of Singapore, National University of Singapore, Singapore. 3Molecular Pathology and 4Growth Factors Groups, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 5Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA. 6Human Oncology and Pathogenesis Program and Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 7Breast Cancer and Melanoma Group and 8Translational Genomics Unit, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 9Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. 10Center for Cancer Genome Discovery, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. 11Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. 12Department of Molecular Genetics and Microbiology, Duke RNAi Screening Facility, Duke University Medical Center, Durham, North Carolina, USA.
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1Experimental Therapeutics, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 2Cancer Science Institute of Singapore, National University of Singapore, Singapore. 3Molecular Pathology and 4Growth Factors Groups, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 5Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA. 6Human Oncology and Pathogenesis Program and Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 7Breast Cancer and Melanoma Group and 8Translational Genomics Unit, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 9Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. 10Center for Cancer Genome Discovery, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. 11Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. 12Department of Molecular Genetics and Microbiology, Duke RNAi Screening Facility, Duke University Medical Center, Durham, North Carolina, USA.
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1Experimental Therapeutics, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 2Cancer Science Institute of Singapore, National University of Singapore, Singapore. 3Molecular Pathology and 4Growth Factors Groups, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 5Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA. 6Human Oncology and Pathogenesis Program and Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 7Breast Cancer and Melanoma Group and 8Translational Genomics Unit, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 9Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. 10Center for Cancer Genome Discovery, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. 11Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. 12Department of Molecular Genetics and Microbiology, Duke RNAi Screening Facility, Duke University Medical Center, Durham, North Carolina, USA.
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1Experimental Therapeutics, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 2Cancer Science Institute of Singapore, National University of Singapore, Singapore. 3Molecular Pathology and 4Growth Factors Groups, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 5Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA. 6Human Oncology and Pathogenesis Program and Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 7Breast Cancer and Melanoma Group and 8Translational Genomics Unit, Vall d’Hebron Institute of Oncology, Barcelona, Spain. 9Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. 10Center for Cancer Genome Discovery, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA. 11Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. 12Department of Molecular Genetics and Microbiology, Duke RNAi Screening Facility, Duke University Medical Center, Durham, North Carolina, USA.
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Published March 3, 2014 - More info
J Clin Invest. 2014;124(3):1418–1418. https://doi.org/10.1172/JCI75534.
© 2014 The American Society for Clinical Investigation
Related article:
Abstract
The PI3K signaling pathway regulates diverse cellular processes, including proliferation, survival, and metabolism, and is aberrantly activated in human cancer. As such, numerous compounds targeting the PI3K pathway are currently being clinically evaluated for the treatment of cancer, and several have shown some early indications of efficacy in breast cancer. However, resistance against these agents, both de novo and acquired, may ultimately limit the efficacy of these compounds. Here, we have taken a systematic functional approach to uncovering potential mechanisms of resistance to PI3K inhibitors and have identified several genes whose expression promotes survival under conditions of PI3K/mammalian target of rapamycin (PI3K/mTOR) blockade, including the ribosomal S6 kinases
Authors
Violeta Serra, Pieter J.A. Eichhorn, Celina García-García, Yasir H. Ibrahim, Ludmila Prudkin, Gertrudis Sánchez, Olga Rodríguez, Pilar Antón, Josep-Lluís Parra, Sara Marlow, Maurizio Scaltriti, José Pérez-Garcia, Aleix Prat, Joaquín Arribas, William C. Hahn, So Young Kim, José Baselga
Original citation: J. Clin. Invest. 2013;123(6):2551–2563. doi:10.1172/JCI66343.
Citation for this corrigendum: J. Clin. Invest. 2014;124(3):1418. doi:10.1172/JCI75534.
The affiliation for Joaquín Arribas was incorrect. The correct affiliation list is above.
The authors regret the error.
Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)