RANK expression and Luminal BC response to CDK4/6 inhibitors
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA931247 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23330843.fastq.gz | Fastqsanger.gz | |||
| SRR23330844.fastq.gz | Fastqsanger.gz | |||
| SRR23330845.fastq.gz | Fastqsanger.gz | |||
| SRR23330846.fastq.gz | Fastqsanger.gz | |||
| SRR23330847.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 15 |
Similar Datasets
Project description:The combination of endocrine therapy (ET) with CDK4/6 inhibitors (CDK4/6i) was the most recent life-changing hallmark in metastatic Luminal breast cancer (BC). However, intrinsic and acquired resistance affect long-term efficacy. Here, we studied the role of receptor activator of nuclear factor-kB (RANK) pathway in CDK4/6i resistance. We found that RANK overexpression in Luminal BC associates with intrinsic resistance to CDK4/6i, both in vitro and in mouse xenografts. Transcriptomic analysis of mouse tumors highlighted decreased proliferation rate and chronic interferon (IFN)-response as resistance drivers.
2023-06-09 | GSE224435 | GEO
Project description:Combining CDK4/6 inhibitors (CDK4/6i) with endocrine therapy has proven clinically effective and represents now the first-line treatment for advanced Luminal Breast Cancer (LBC) patients. However, resistance to CDK4/6i almost invariably arises in these patients, emphasising the critical need to comprehend these mechanisms and develop new strategies to overcome resistance. We report on the generation and characterisation of a LBC PDX displaying acquired resistance to CDK4/6i palbociclib. Treating a sensitive luminal BC PDX with the CDK4/6i palbociclib revealed that, despite initial tumour shrinkage, some tumours might eventually regrow under drug treatment. RNA sequencing, followed by gene set enrichment analyses, unveiled that this PDX have become refractory to CDK4/6i, both at biological and molecular level.
2024-11-18 | E-MTAB-14085 | biostudies-arrayexpress
Project description:Resistance to CDK4/6 inhibitors leads to treatment failure and disease progression in women with HR+HER2- breast cancer (BC). We delineated a hypoxia-sensitive, CCL2-dependent pathway recruiting IL17A-secreting γδ T cells to mouse HR+HER2- BCs upon CDK4/6 inhibition, resulting in repolarization of tumor-associated macrophages (TAMs) towards an immunosuppressive CX3CR1+ phenotype associated with resistance. Increased IL17A signaling and intratumoral γδ T cell abundance positively correlated with advanced grade and/or reduced survival in two cohorts of HR+HER2- BC patients. Circulating γδ T cells and plasma CCL2 levels negatively correlated with progression in an independent series of patients with HR+HER2- BC receiving CDK4/6 inhibitors. Intratumoral γδ T cells were increased in post- vs pre-treatment biopsies from HR+HER2- BC patients relapsing on CDK4/6 inhibitors. CX3CR1+ TAMs had negative prognostic impact in women with HR+HER2- BC receiving neoadjuvant PD-1 blockage and radiotherapy. Thus, γδ T cells and CX3XR1+ TAMs may favor resistance to CDK4/6 inhibitors in HR+HER2- BC patients.
2025-05-09 | GSE296805 | GEO
Project description:Resistance to CDK4/6 inhibitors leads to treatment failure and disease progression in women with HR+HER2- breast cancer (BC). We delineated a hypoxia-sensitive, CCL2-dependent pathway recruiting IL17A-secreting γδ T cells to mouse HR+HER2- BCs upon CDK4/6 inhibition, resulting in repolarization of tumor-associated macrophages (TAMs) towards an immunosuppressive CX3CR1+ phenotype associated with resistance. Increased IL17A signaling and intratumoral γδ T cell abundance positively correlated with advanced grade and/or reduced survival in two cohorts of HR+HER2- BC patients. Circulating γδ T cells and plasma CCL2 levels negatively correlated with progression in an independent series of patients with HR+HER2- BC receiving CDK4/6 inhibitors. Intratumoral γδ T cells were increased in post- vs pre-treatment biopsies from HR+HER2- BC patients relapsing on CDK4/6 inhibitors. CX3CR1+ TAMs had negative prognostic impact in women with HR+HER2- BC receiving neoadjuvant PD-1 blockage and radiotherapy. Thus, γδ T cells and CX3XR1+ TAMs may favor resistance to CDK4/6 inhibitors in HR+HER2- BC patients.
2025-05-09 | GSE296798 | GEO
Project description:RANK-positive and RANK-negative luminal progenitor cells were isolated by FACS from histologically normal human breast tissue from wild-type human donors. RNA-seq gene expression profiling was used to find differentially expressed genes between the RANK-positive and RANK-negative cell populations.
2016-06-20 | GSE71203 | GEO
Project description:CDK4/6i alone have proven to be largely ineffective in TNBC, even in the presence of functional retinoblastoma protein (pRB). In this study, we investigated the role of the RANK pathway in the response to CDK4/6i in pRB-proficient TNBC. Transcriptomic analysis of xenografts revealed that combining CDK4/6i with RANKLi more effectively arrested the cell cycle.
2025-05-20 | GSE277615 | GEO
Project description:CDK4/6i alone have proven to be largely ineffective in breast cancer, even in the presence of functional retinoblastoma protein (pRB). In this study, we investigated the role of the RANK pathway in the response to CDK4/6i in pRB-proficient TNBC. Transcriptomic analysis of allografts revealed that combining CDK4/6i with RANKLi more effectively mounts an anti-tumoral immune response.
2025-05-20 | GSE277614 | GEO
Project description:CDK4/6 inhibitors are highly effective against ER+/HER2- breast cancer (BC); however, intrinsic and acquired resistance is common. Elucidating the molecular features of sensitivity and resistance to CDK4/6 inhibitors may lead to the identification of predictive biomarkers and novel therapeutic targets, paving the way toward improving patient outcomes. Parental BC cells and their endocrine-resistant derivatives (EndoR) were used in this study. Derivatives with acquired resistance to palbociclib (PalboR) were generated from parental and estrogen deprivation-resistant MCF7 and T47D cells. Transcriptomic and proteomic analyses were performed in palbociclib-sensitive and PalboR lines. We found that parental and EndoR BC lines showed varying degrees of sensitivity to palbociclib. Transcriptomic analysis of these cell lines identified an association between high Interferon (IFN) signaling and reduced sensitivity to CDK4/6 inhibitors, thus an ‘IFN-Related Palbociclib-Resistance Signature’ (IRPS) was derived. In two neoadjuvant trials of a CDK4/6 inhibitor plus endocrine therapy, IRPS and other IFN-related signatures were highly enriched in patients with tumors exhibiting intrinsic resistance to CDK4/6 inhibition. PalboR derivatives displayed a dramatic activation of IFN/STAT1-signaling compared to their short-term treated or untreated counterparts. In primary ER+/HER2- tumors, the IRPS score was significantly higher in lumB than lumA subtype and correlated with increased gene expression of immune checkpoints, endocrine resistance, and poor prognosis. Our study demonstrates that aberrant IFN-signaling is associated with intrinsic resistance to CDK4/6 inhibitors. Experimentally, acquired resistance to palbociclib is associated with activation of the IFN-pathway, which warrants additional studies to clarify its involvement in resistance to CDK4/6 inhibitors.
2021-12-04 | GSE150997 | GEO
Project description:TNBC response to CDK4/6 inhibitors plus RANKL inhibitors
| PRJNA1162906 | ENA
Project description:Despite significant improvement in therapeutic development in the past decades, breast cancer remains a formidable cause of death for women worldwide. The hormone positive subtype (HR(+)) (also known as luminal type) is the most prevalant category of breast cancer, comprising ~70% of patients. The clinical success of the three CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib has revolutionzied the treatment of choice for metastatic HR(+) breast cancer. Accumulating evidence demonstrate that the properties of CDK4/6 inhibitors extend beyond inhibition of the cell cycle, including modulation of immune function , sensitizing PI3K inhibitors, metabolism reprogramming , kinome rewiring, modulation of the proteosome, and many others. The ubiquitin–proteasome pathway (UPP) is a crucial cellular proteolytic system that maintains the homeostasis and turnover of proteins. By transcriptional profiling of the HR(+) breast cancer cell lines treated with the three CDK4/6 inhibitors, we have uncovered a novel mechanism that demonstrate the CDK4/6 inhibitors suppress the expression of three ubiquitin conjugating enzymes UBE2C, UBE2S, UBE2T. These three E2 enzymes modulate a number of E3 ubiquitin ligases, including the APC/C complex which plays a role in G1/S progression. Our study provide a novel link between CDK4/6 inhibitor and UPP which could have important implications in cancer biology.
2022-04-23 | GSE201113 | GEO