| http://purl.uniprot.org/citations/34932500 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34932500 | http://www.w3.org/2000/01/rdf-schema#comment | "Standard radiation therapy (RT) does not reliably provide locoregional control for women with multinode-positive breast cancer and triple-negative breast cancer (TNBC). We hypothesized that CDK4/6 inhibition (CDK4/6i) would increase the radiosensitivity not only of estrogen receptor-positive (ER+) cells, but also of TNBC that expresses retinoblastoma (RB) protein. We found that CDK4/6i radiosensitized RB WT TNBC (n = 4, radiation enhancement ratio [rER]: 1.49-2.22) but failed to radiosensitize RB-null TNBC (n = 3, rER: 0.84-1.00). RB expression predicted response to CDK4/6i + RT (R2 = 0.84), and radiosensitization was lost in ER+/TNBC cells (rER: 0.88-1.13) after RB1 knockdown in isogenic and nonisogenic models. CDK4/6i suppressed homologous recombination (HR) in RB WT cells but not in RB-null cells or isogenic models of RB1 loss; HR competency was rescued with RB reexpression. Radiosensitization was independent of nonhomologous end joining and the known effects of CDK4/6i on cell cycle arrest. Mechanistically, RB and RAD51 interact in vitro to promote HR repair. CDK4/6i produced RB-dependent radiosensitization in TNBC xenografts but not in isogenic RB1-null xenografts. Our data provide the preclinical rationale for a clinical trial expanding the use of CDK4/6i + RT to difficult-to-control RB-intact breast cancers (including TNBC) and nominate RB status as a predictive biomarker of therapeutic efficacy."xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci.insight.154402"xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://purl.uniprot.org/core/author | "Liu M."xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://purl.uniprot.org/core/author | "Ward C."xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://purl.uniprot.org/core/author | "Lawrence T.S."xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://purl.uniprot.org/core/author | "Rae J.M."xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://purl.uniprot.org/core/author | "Pierce L.J."xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://purl.uniprot.org/core/author | "Wilder-Romans K."xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://purl.uniprot.org/core/author | "Nino C.A."xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://purl.uniprot.org/core/author | "Pesch A.M."xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://purl.uniprot.org/core/author | "Chandler B.C."xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://purl.uniprot.org/core/author | "Michmerhuizen A.R."xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://purl.uniprot.org/core/author | "Cobain E.F."xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://purl.uniprot.org/core/author | "Hirsh N.H."xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://purl.uniprot.org/core/author | "Jungles K.M."xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://purl.uniprot.org/core/author | "Lerner L.M."xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://purl.uniprot.org/core/author | "Speers C.W."xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/34932500 | http://purl.uniprot.org/core/name | "JCI Insight"xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://purl.uniprot.org/core/pages | "e154402"xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://purl.uniprot.org/core/title | "RB expression confers sensitivity to CDK4/6 inhibitor-mediated radiosensitization across breast cancer subtypes."xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://purl.uniprot.org/core/volume | "7"xsd:string |
| http://purl.uniprot.org/citations/34932500 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/34932500 |
| http://purl.uniprot.org/citations/34932500 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/34932500 |