dc.contributor.author | Palafox, M | |
dc.contributor.author | Monserrat, L | |
dc.contributor.author | Bellet, M | |
dc.contributor.author | Villacampa, G | |
dc.contributor.author | Gonzalez-Perez, A | |
dc.contributor.author | Oliveira, M | |
dc.contributor.author | Brasó-Maristany, F | |
dc.contributor.author | Ibrahimi, N | |
dc.contributor.author | Kannan, S | |
dc.contributor.author | Mina, L | |
dc.contributor.author | Herrera-Abreu, MT | |
dc.contributor.author | Òdena, A | |
dc.contributor.author | Sánchez-Guixé, M | |
dc.contributor.author | Capelán, M | |
dc.contributor.author | Azaro, A | |
dc.contributor.author | Bruna, A | |
dc.contributor.author | Rodríguez, O | |
dc.contributor.author | Guzmán, M | |
dc.contributor.author | Grueso, J | |
dc.contributor.author | Viaplana, C | |
dc.contributor.author | Hernández, J | |
dc.contributor.author | Su, F | |
dc.contributor.author | Lin, K | |
dc.contributor.author | Clarke, RB | |
dc.contributor.author | Caldas, C | |
dc.contributor.author | Arribas, J | |
dc.contributor.author | Michiels, S | |
dc.contributor.author | García-Sanz, A | |
dc.contributor.author | Turner, NC | |
dc.contributor.author | Prat, A | |
dc.contributor.author | Nuciforo, P | |
dc.contributor.author | Dienstmann, R | |
dc.contributor.author | Verma, CS | |
dc.contributor.author | Lopez-Bigas, N | |
dc.contributor.author | Scaltriti, M | |
dc.contributor.author | Arnedos, M | |
dc.contributor.author | Saura, C | |
dc.contributor.author | Serra, V | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2022-12-14T09:24:56Z | |
dc.date.available | 2022-12-14T09:24:56Z | |
dc.date.issued | 2022-09-07 | |
dc.identifier | ARTN 5258 | |
dc.identifier | 10.1038/s41467-022-32828-6 | |
dc.identifier.citation | Nature Communications, 2022, 13 (1), pp. 5258 - | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5606 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-022-32828-6 | |
dc.description.abstract | 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. | |
dc.format | Electronic | |
dc.format.extent | 5258 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.relation.ispartof | Nature Communications | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Antineoplastic Agents | |
dc.subject | Biomarkers | |
dc.subject | Breast Neoplasms | |
dc.subject | Cyclin-Dependent Kinase 4 | |
dc.subject | Cyclin-Dependent Kinase 6 | |
dc.subject | Drug Resistance, Neoplasm | |
dc.subject | Female | |
dc.subject | Humans | |
dc.subject | Phosphatidylinositol 3-Kinases | |
dc.subject | Protein Kinase Inhibitors | |
dc.subject | Receptors, Estrogen | |
dc.subject | Retinoblastoma Binding Proteins | |
dc.subject | Ubiquitin-Protein Ligases | |
dc.title | High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER+ breast cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-08-17 | |
dc.date.updated | 2022-12-14T09:23:43Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/s41467-022-32828-6 | |
rioxxterms.licenseref.startdate | 2022-09-07 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/36071033 | |
pubs.issue | 1 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1038/s41467-022-32828-6 | |
pubs.volume | 13 | |
icr.researchteam | Molecular Oncology | |
dc.contributor.icrauthor | Bruna Cabot, Alejandra | |
dc.contributor.icrauthor | Turner, Nicholas | |
icr.provenance | Deposited by Mr Arek Surman on 2022-12-14. Deposit type is initial. No. of files: 1. Files: High p16 expression and heterozygous RB1 loss are biomarkers for CDK46 inhibitor resistance in ERsup+sup breast cancer.pdf | |