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
5368 - Durvalumab and Paclitaxel Combination for treatment of metastatic triple negative breast cancer is safe with very promising efficacy
Presenter: Hazem Ghebeh
Session: Poster Display session 3
Resources:
Abstract
1520 - A prospective cohort study on the pharmacokinetics of nivolumab in metastatic non-small cell lung cancer, melanoma, and renal cell cancer patients
Presenter: Daan Hurkmans
Session: Poster Display session 3
Resources:
Abstract
1603 - Safety and clinical activity of subcutaneously (SC) administered anti-PD-1 antibody PF-06801591 in phase I dose-expansion cohorts of locally advanced or metastatic non-small-cell lung cancer (NSCLC) and urothelial carcinoma (UC)
Presenter: Byoung Cho
Session: Poster Display session 3
Resources:
Abstract
3922 - Development of the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM): A scale to measure quality of life in cancer patients treated with ICMs
Presenter: Aaron Hansen
Session: Poster Display session 3
Resources:
Abstract
2408 - Immune checkpoint inhibitors (ICIs) as “chemotherapy (Ctx) sensitization” strategy in advanced solid tumors
Presenter: Francisco Javier Ros Montana
Session: Poster Display session 3
Resources:
Abstract
3612 - Validation of progression-free survival (PFS) as surrogate endpoint in randomised trials of immune checkpoint inhibitors in advanced solid cancers
Presenter: Peey Sei Kok
Session: Poster Display session 3
Resources:
Abstract
3827 - Pharmacokinetic (PK) analysis of weight-based and fixed dose cemiplimab in patients (pts) with advanced malignancies
Presenter: Michael Migden
Session: Poster Display session 3
Resources:
Abstract
2120 - A burst of highly differentiated CD4 TL identifies a subset of fast progressors, and correlates with hyperprogressive disease in NSCLC patients treated with ICI
Presenter: Hugo Arasanz
Session: Poster Display session 3
Resources:
Abstract
4254 - Nivolumab treatment in advanced non-small cell lung cancer (aNSCLC): a French nationwide retrospective cohort (UNIVOC Study)
Presenter: Christos Chouaid
Session: Poster Display session 3
Resources:
Abstract
1084 - Dissociated responses in patients with metastatic solid tumors treated with immunotherapy
Presenter: Pauline Vaflard
Session: Poster Display session 3
Resources:
Abstract