Therapeutic targeting of HER2–CB2R heteromers in HER2-positive breast cancer

Sandra Blasco-Benito; Estefanía Moreno; Marta  Seijo-Vila; Isabel Tundidor; Clara Andradas; María M. Caffarel; Miriam  Caro-Villalobos; Leyre Urigüen; Rebeca Diez-Alarcia; Gema Moreno-Bueno; Lucía  Hernández; Luis  Manso; Patricia  Homar-Ruano; Peter J. McCormick; Lucka Bibic; Cristina  Bernadó-Morales; Joaquín  Arribas; Meritxell  Canals; Vicent Casadó; Enric Isidre Canela; Manuel Guzmán; Eduardo Pérez-Gómez; Cristina Sánchez

doi:10.1073/pnas.1815034116

Therapeutic targeting of HER2–CB2R heteromers in HER2-positive breast cancer

Sandra Blasco-Benito, Estefanía Moreno, Marta Seijo-Vila, Isabel Tundidor, Clara Andradas, María M. Caffarel, Miriam Caro-Villalobos, Leyre Urigüen, Rebeca Diez-Alarcia, Gema Moreno-Bueno, Lucía Hernández, Luis Manso, Patricia Homar-Ruano, Peter J. McCormick, Lucka Bibic, Cristina Bernadó-Morales, Joaquín Arribas, Meritxell Canals, Vicent Casadó, Enric Isidre CanelaManuel Guzmán, Eduardo Pérez-Gómez, Cristina Sánchez

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Abstract

There is a subtype of breast cancer characterized by the overexpression of the oncogene HER2. Although most patients with this diagnosis benefit from HER2-targeted treatments, some do not respond to these therapies and others develop resistance with time. New tools are therefore warranted for the treatment of this patient population, and for early identification of those individuals at a higher risk of developing innate or acquired resistance to current treatments. Here, we show that HER2 forms heteromer complexes with the cannabinoid receptor CB2R, the expression of these structures correlates with poor patient prognosis, and their disruption promotes antitumor responses. Collectively, our results support HER2–CB2R heteromers as new therapeutic targets and prognostic tools in HER2+ breast cancer.

Original language	English
Pages (from-to)	3863-3872
Number of pages	10
Journal	Proceedings of the National Academy of Sciences of the United States of America (PNAS)
Volume	116
Issue number	9
Early online date	7 Feb 2019
DOIs	https://doi.org/10.1073/pnas.1815034116
Publication status	Published - 26 Feb 2019

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10.1073/pnas.1815034116

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Cite this

Blasco-Benito, S., Moreno, E., Seijo-Vila, M., Tundidor, I., Andradas, C., Caffarel, M. M., Caro-Villalobos, M., Urigüen, L., Diez-Alarcia, R., Moreno-Bueno, G., Hernández, L., Manso, L., Homar-Ruano, P., McCormick, P. J., Bibic, L., Bernadó-Morales, C., Arribas, J., Canals, M., Casadó, V., ... Sánchez, C. (2019). Therapeutic targeting of HER2–CB2R heteromers in HER2-positive breast cancer. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 116(9), 3863-3872. https://doi.org/10.1073/pnas.1815034116

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title = "Therapeutic targeting of HER2–CB2R heteromers in HER2-positive breast cancer",

abstract = "There is a subtype of breast cancer characterized by the overexpression of the oncogene HER2. Although most patients with this diagnosis benefit from HER2-targeted treatments, some do not respond to these therapies and others develop resistance with time. New tools are therefore warranted for the treatment of this patient population, and for early identification of those individuals at a higher risk of developing innate or acquired resistance to current treatments. Here, we show that HER2 forms heteromer complexes with the cannabinoid receptor CB2R, the expression of these structures correlates with poor patient prognosis, and their disruption promotes antitumor responses. Collectively, our results support HER2–CB2R heteromers as new therapeutic targets and prognostic tools in HER2+ breast cancer.",

author = "Sandra Blasco-Benito and Estefan{\'i}a Moreno and Marta Seijo-Vila and Isabel Tundidor and Clara Andradas and Caffarel, {Mar{\'i}a M.} and Miriam Caro-Villalobos and Leyre Urig{\"u}en and Rebeca Diez-Alarcia and Gema Moreno-Bueno and Luc{\'i}a Hern{\'a}ndez and Luis Manso and Patricia Homar-Ruano and McCormick, {Peter J.} and Lucka Bibic and Cristina Bernad{\'o}-Morales and Joaqu{\'i}n Arribas and Meritxell Canals and Vicent Casad{\'o} and Canela, {Enric Isidre} and Manuel Guzm{\'a}n and Eduardo P{\'e}rez-G{\'o}mez and Cristina S{\'a}nchez",

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Blasco-Benito, S, Moreno, E, Seijo-Vila, M, Tundidor, I, Andradas, C, Caffarel, MM, Caro-Villalobos, M, Urigüen, L, Diez-Alarcia, R, Moreno-Bueno, G, Hernández, L, Manso, L, Homar-Ruano, P, McCormick, PJ, Bibic, L, Bernadó-Morales, C, Arribas, J, Canals, M, Casadó, V, Canela, EI, Guzmán, M, Pérez-Gómez, E & Sánchez, C 2019, 'Therapeutic targeting of HER2–CB2R heteromers in HER2-positive breast cancer', Proceedings of the National Academy of Sciences of the United States of America (PNAS), vol. 116, no. 9, pp. 3863-3872. https://doi.org/10.1073/pnas.1815034116

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T1 - Therapeutic targeting of HER2–CB2R heteromers in HER2-positive breast cancer

AU - Blasco-Benito, Sandra

AU - Moreno, Estefanía

AU - Seijo-Vila, Marta

AU - Tundidor, Isabel

AU - Andradas, Clara

AU - Caffarel, María M.

AU - Caro-Villalobos, Miriam

AU - Urigüen, Leyre

AU - Diez-Alarcia, Rebeca

AU - Moreno-Bueno, Gema

AU - Hernández, Lucía

AU - Manso, Luis

AU - Homar-Ruano, Patricia

AU - McCormick, Peter J.

AU - Bibic, Lucka

AU - Bernadó-Morales, Cristina

AU - Arribas, Joaquín

AU - Canals, Meritxell

AU - Casadó, Vicent

AU - Canela, Enric Isidre

AU - Guzmán, Manuel

AU - Pérez-Gómez, Eduardo

AU - Sánchez, Cristina

N1 - Erratum at: 10.1073/pnas.1903209116

PY - 2019/2/26

Y1 - 2019/2/26

N2 - There is a subtype of breast cancer characterized by the overexpression of the oncogene HER2. Although most patients with this diagnosis benefit from HER2-targeted treatments, some do not respond to these therapies and others develop resistance with time. New tools are therefore warranted for the treatment of this patient population, and for early identification of those individuals at a higher risk of developing innate or acquired resistance to current treatments. Here, we show that HER2 forms heteromer complexes with the cannabinoid receptor CB2R, the expression of these structures correlates with poor patient prognosis, and their disruption promotes antitumor responses. Collectively, our results support HER2–CB2R heteromers as new therapeutic targets and prognostic tools in HER2+ breast cancer.

AB - There is a subtype of breast cancer characterized by the overexpression of the oncogene HER2. Although most patients with this diagnosis benefit from HER2-targeted treatments, some do not respond to these therapies and others develop resistance with time. New tools are therefore warranted for the treatment of this patient population, and for early identification of those individuals at a higher risk of developing innate or acquired resistance to current treatments. Here, we show that HER2 forms heteromer complexes with the cannabinoid receptor CB2R, the expression of these structures correlates with poor patient prognosis, and their disruption promotes antitumor responses. Collectively, our results support HER2–CB2R heteromers as new therapeutic targets and prognostic tools in HER2+ breast cancer.

U2 - 10.1073/pnas.1815034116

DO - 10.1073/pnas.1815034116

M3 - Article

SN - 1091-6490

VL - 116

SP - 3863

EP - 3872

JO - Proceedings of the National Academy of Sciences of the United States of America (PNAS)

JF - Proceedings of the National Academy of Sciences of the United States of America (PNAS)

IS - 9

ER -