Abstract 4357
Background
Triple negative breast cancers (TNBC) are enriched with cells bearing stem-like features (CSC), which underlie cancer progression, thus targeting stemness could be an interesting treatment approach. In turn, the epigenetic machinery is crucial for the maintenance of the stemness phenotype. The BET family of epigenetic readers are emerging as novel targets for cancer therapy and have shown preclinical effect in breast cancer. In this work we evaluate the effect of the BET inhibitor (BETi) JQ1 on stemness in TNBC.
Methods
Transcriptomic, functional annotation and qPCR studies were performed on JQ1-exposed TNBC cells. Results were confirmed on spheroids and spheroid-derived tumours. Limiting dilution assays, matrigel invasion experiments, immunofluorescence staining, and flow cytometry studies were also performed to evaluate the effect of JQ1 on CSC features. For the outcome analysis, the online tool Kaplan-Meier Plotter and an integrated response database were used.
Results
JQ1 can modify the expression of stemness-related genes incultured TNBC cells. Among these changes, the CD44/CD24 and ALDH1A1 expression, both classical stemness markers, were diminished by JQ1. Using a validated spheroid model, to mimic the intrinsic characteristics of CSCs, we show that JQ1 decreased surface expression of CD44, inhibited self-renewal and invasion, and induced cells arrest in G0/G1, therefore altering the stemness phenotype in TNBC. Four of the identified stemness genes, GJA1, CD24, EPCAM, and SOX9, were found to be associated with worse patient outcome in TNBC. Furthermore, ABCG2 and RUNX2 predicted low response to chemotherapy in TNBC patients.
Conclusions
In this work we show how BETi modify the stemness landscape in TNBC. Thus, we propose a novel role for JQ1 as a stemness-targeting drug. Loss of the stem cell phenotype via JQ1 treatment could lead to less aggressive and more chemo-sensitive tumours, which would reflect in better patient prognosis.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5705 - External validation and longitudinal extension of the LIPI (Lung Immune Prognostic Index) for immunotherapy outcomes in advanced non-small cell lung cancer.
Presenter: Jakob Riedl
Session: Poster Display session 3
Resources:
Abstract
5758 - Changes of TCR Repertoire in Metastatic Renal Cell Carcinoma and Metastatic Melanoma Patients Treated with Nivolumab
Presenter: Martin Klabusay
Session: Poster Display session 3
Resources:
Abstract
1743 - Expression of MHC class I, HLA-A and HLA-B identifies immune activated breast tumors with favorable outcome
Presenter: María Del Mar Noblejas López
Session: Poster Display session 3
Resources:
Abstract
2219 - Prognostic Significance of Tumor Tissue NeuGcGM3 Ganglioside Expression and Predictive Value of Circulating Tumor Cell Count Monitoring in Patients Receiving Racotumomab Immunotherapy
Presenter: Necdet Üskent
Session: Poster Display session 3
Resources:
Abstract
2996 - Evolution of Myeloid-Derived Suppressor Cells and Objective Response Rate in Relapsed/Refractory Diffuse Large B Cell Lymphoma (R/R DLBCL) patients after receiving immunotherapy
Presenter: Carlos Jiménez Cortegana
Session: Poster Display session 3
Resources:
Abstract
2110 - A Phase Ia/Ib trial of the anti-programmed death-ligand 1 (PD-L1) human monoclonal antibody (mAb), CS1001, in patients (pts) with advanced solid tumors or lymphomas
Presenter: Lin Shen
Session: Poster Display session 3
Resources:
Abstract
3515 - Results from a randomised Phase 1/2 trial evaluating the safety and antitumour activity of anti-PD-1 (MEDI0680)/anti-PD-L1 (durvalumab) vs anti-PD-1 (nivolumab) alone in metastatic clear cell renal cell carcinoma (ccRCC)
Presenter: Martin Voss
Session: Poster Display session 3
Resources:
Abstract
3566 - Pembrolizumab in Advanced Rare Cancers
Presenter: Aung Naing
Session: Poster Display session 3
Resources:
Abstract
3567 - High clinical benefit rates of pembrolizumab in very rare sarcoma histotypes: first results of the AcSé Pembrolizumab study
Presenter: Jean-Yves Blay
Session: Poster Display session 3
Resources:
Abstract
2421 - Lenvatinib plus PD-1 blockade in advanced bile tract carcinoma.
Presenter: Jianzhen Lin
Session: Poster Display session 3
Resources:
Abstract