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
3489 - Overall Survival (OS) and Metastasis-Free Survival (MFS) in men with Biochemically Relapsed (BCR) Prostate Cancer after radical prostatectomy (RP) managed with deferred Androgen Deprivation Treatment (ADT): A combined Johns Hopkins and CPDR study
Presenter: Catherine Marshall
Session: Poster Display session 3
Resources:
Abstract
4606 - ARCHES – the role of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): Post hoc analyses of high and low disease volume and risk groups
Presenter: Arnulf Stenzl
Session: Poster Display session 3
Resources:
Abstract
2975 - Updated survival analyses of a multicentric phase II randomized trial of docetaxel (D) plus enzalutamide (E) versus docetaxel (D) as first line chemotherapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) (CHEIRON study).
Presenter: Orazio Caffo
Session: Poster Display session 3
Resources:
Abstract
2708 - Real-world analysis of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving vs not receiving chemotherapy in the treatment sequence
Presenter: Alicia Morgans
Session: Poster Display session 3
Resources:
Abstract
2134 - Baseline fracture risk in men with prostate cancer starting the STAMPEDE trial
Presenter: Janet Brown
Session: Poster Display session 3
Resources:
Abstract
3504 - Risk of falls and fractures in patients with castration resistant prostate cancer (CRPC) treated with new hormonal agents – a meta-analysis of randomized controlled trials.
Presenter: Rodrigo Coutinho Mariano
Session: Poster Display session 3
Resources:
Abstract
2342 - Pain progression at initiation of chemotherapy in metastatic Castration-Resistant Prostate Cancer (mCRPC) is associated with a poor prognosis: a post-hoc analysis of FIRSTANA
Presenter: Nicolas Delanoy
Session: Poster Display session 3
Resources:
Abstract
5331 - Pain evaluation in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (Ra-223) in the PARABO observation study
Presenter: Holger Palmedo
Session: Poster Display session 3
Resources:
Abstract
2823 - Time to castration resistant prostate cancer (CRPC) and the risk of developing immune disorders
Presenter: Vincenza Conteduca
Session: Poster Display session 3
Resources:
Abstract
1500 - Retrospective evaluation of neutropenic admission events in metastatic or high-risk hormone-sensitive prostate cancer (HSPC) patients having docetaxel chemotherapy upfront or for castrate-resistant prostate cancer (CRPC) in STAMPEDE
Presenter: Harriet Mintz
Session: Poster Display session 3
Resources:
Abstract