Carregant...
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/197341
High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER<sup>+</sup> breast cancer
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Resum
CDK4/6 inhibitors combined with endocrine therapy have demonstrated higher antitumor activity than endocrine therapy alone for the treatment of advanced estrogen receptor-positive breast cancer. Some of these tumors are de novo resistant to CDK4/6 inhibitors and others develop acquired resistance. Here, we show that p16 overexpression is associated with reduced antitumor activity of CDK4/6 inhibitors in patient-derived xenografts (n?=?37) and estrogen receptor-positive breast cancer cell lines, as well as reduced response of early and advanced breast cancer patients to CDK4/6 inhibitors (n?=?89). We also identified heterozygous RB1 loss as biomarker of acquired resistance and poor clinical outcome. Combination of the CDK4/6 inhibitor ribociclib with the PI3K inhibitor alpelisib showed antitumor activity in estrogen receptor-positive non-basal-like breast cancer patient-derived xenografts, independently of PIK3CA, ESR1 or RB1 mutation, also in drug de-escalation experiments or omitting endocrine therapy. Our results offer insights into predicting primary/acquired resistance to CDK4/6 inhibitors and post-progression therapeutic strategies.© 2022. The Author(s).
Matèries (anglès)
Citació
Citació
PALAFOX SÁNCHEZ, Marta, MONSERRAT VICENTE, Laia, BELLET EZQUERRA, Meritxell, VILLACAMPA, Guillermo, GONZÁLEZ PÉREZ, Abel, OLIVEIRA, Mafalda, BRASÓ MARISTANY, Fara, IBRAHIMI, Nusaibah, KANNAN, Srinivasaraghavan, MINA, Leonardo, HERRERA ABREU, Maria teresa, ODENA, Andreu, SÁNCHEZ GUIXÉ, Mònica, CAPELÁN, Marta, AZARO, Analía, BRUNA, Alejandra, RODRIGUEZ, Olga, GUZMÁN, Marta, GRUESO, Judit, VIAPLANA, Cristina, HERNANDEZ, Javier, SU, Faye, LIN, Kui, CLARKE, Robert, CALDAS, Carlos, ARRIBAS, Joaquín, MICHIELS, Stefan, GARCÍA SANZ, Alicia, TURNER, Nicholas, PRAT APARICIO, Aleix, NUCIFORO, Paolo, DIENSTMANN, Rodrigo, VERMA, Chandra s, LÓPEZ BIGAS, Núria, SCALTRITI, Maurizio, ARNEDOS, Monica, SAURA, Cristina, SERRA ELIZALDE, Violeta. High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER<sup>+</sup> breast cancer. _Nature Communications_. 2022. Vol. 13. [consulta: 2 de febrer de 2026]. ISSN: 2041-1723. [Disponible a: https://hdl.handle.net/2445/197341]