Abstract P5-03-10: Circulating exosomal microRNA profiling to depict mechanisms of chemotherapy resistance among triple negative breast cancer

2019 ◽  
Author(s):  
Y He ◽  
J Tang
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Chemotherapy Resistance ◽  
Microrna Profiling ◽  
Exosomal Microrna

scholarly journals Simultaneous CK2/TNIK/DYRK1 inhibition by 108600 suppresses triple negative breast cancer stem cells and chemotherapy-resistant disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Katsutoshi Sato ◽  
Amol A. Padgaonkar ◽  
Stacey J. Baker ◽  
Stephen C. Cosenza ◽  
Olga Rechkoblit ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Kinase Inhibitor ◽  
Chemotherapy Resistance ◽  
Metastatic Progression ◽  
Resistant Disease ◽  
Risk Patients ◽  
Additional Support

AbstractTriple negative breast cancer (TNBC) remains challenging because of heterogeneous responses to chemotherapy. Incomplete response is associated with a greater risk of metastatic progression. Therefore, treatments that target chemotherapy-resistant TNBC and enhance chemosensitivity would improve outcomes for these high-risk patients. Breast cancer stem cell-like cells (BCSCs) have been proposed to represent a chemotherapy-resistant subpopulation responsible for tumor initiation, progression and metastases. Targeting this population could lead to improved TNBC disease control. Here, we describe a novel multi-kinase inhibitor, 108600, that targets the TNBC BCSC population. 108600 treatment suppresses growth, colony and mammosphere forming capacity of BCSCs and induces G2M arrest and apoptosis of TNBC cells. In vivo, 108600 treatment of mice bearing triple negative tumors results in the induction of apoptosis and overcomes chemotherapy resistance. Finally, treatment with 108600 and chemotherapy suppresses growth of pre-established TNBC metastases, providing additional support for the clinical translation of this agent to clinical trials.

scholarly journals Neoadjuvant Therapy in Operable Breast Cancer: Application to Triple Negative Breast Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Foluso O. Ademuyiwa ◽  
Matthew J. Ellis ◽  
Cynthia X. Ma
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Chemotherapy Resistance ◽  
Treatment Strategies ◽  
Surrogate Endpoint ◽  
Complete Response

Systemic treatment for triple negative breast cancer (TNBC: negative for the expression of estrogen receptor and progesterone receptor and HER2 amplification) has been limited to chemotherapy options. Neoadjuvant chemotherapy induces tumor shrinkage and improves the surgical outcomes of patients with locally advanced disease and also identifies those at high risk of disease relapse despite today’s standard of care. By using pathologic complete response as a surrogate endpoint, novel treatment strategies can be efficiently assessed. Tissue analysis in the neoadjuvant setting is also an important research tool for the identification of chemotherapy resistance mechanisms and new therapeutic targets. In this paper, we review data on completed and ongoing neoadjuvant clinical trials in patients with TNBC and discuss treatment controversies that face clinicians and researchers when neoadjuvant chemotherapy is employed.

MicroRNA profiling of triple negative breast cancer: predicting outcome and targets.

2009 ◽  
Author(s):  
TS Paranjape ◽  
SV Nallur ◽  
K Keanie ◽  
M Martel ◽  
BG Haffty ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Microrna Profiling ◽  
Predicting Outcome

scholarly journals Targeted Therapies in Triple-Negative Breast Cancer

Breast Care ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. 159-166 ◽  
Author(s):  
Frederik Marmé ◽  
Andreas Schneeweiss
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Triple Negative Breast Cancer ◽  
Targeted Therapies ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Chemotherapy Resistance ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Receptor Subtype

Triple-negative breast cancer (TNBC) is a heterogeneous disease comprised of several biologically distinct subtypes. However, treatment is currently mainly relying on chemotherapy as there are no targeted therapies specifically approved for TNBC. Despite initial responses to chemotherapy, resistance frequently and rapidly develops and metastatic TNBC has a poor prognosis. New targeted approaches are, therefore, urgently needed. Currently, bevacizumab, a monoclonal anti-vascular endothelial growth factor (VEGF)-A antibody, is the only targeted agent with an approval for the therapy of metastatic breast cancer, but does not provide a specific benefit in the TNBC subtype. This review discusses the current clinical developments in targeted approaches for TNBC, including anti-angiogenic therapies, epidermal growth factor receptor (EGFR)-targeted therapies, poly(ADP-ribose) polymerase (PARP) inhibitors and platinum salts, as well as novel strategies using immune-checkpoint inhibitors, which have recently demonstrated first promising results. Strategies focusing on specific subtypes of TNBC like anti-androgenic therapies for the luminal androgen receptor subtype (LAR) and others are also discussed.

scholarly journals Liver x receptor alpha drives chemoresistance in response to side-chain hydroxycholesterols in triple negative breast cancer

2020 ◽  
Author(s):  
Samantha A Hutchinson ◽  
Alex Websdale ◽  
Giorgia Cioccoloni ◽  
Hanne Røberg-Larsen ◽  
Priscilia Lianto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Chemotherapy Resistance ◽  
Resistance Mechanism ◽  
P Glycoprotein ◽  
Tumor Tissues ◽  
X Receptors ◽  
Necessary And Sufficient

AbstractTriple negative breast cancer (TNBC) is challenging to treat successfully because targeted therapies do not exist. Instead, systemic therapy is typically restricted to cytotoxic chemotherapy, which fails more often in patients with elevated circulating cholesterol. Liver x receptors are ligand-dependent transcription factors that are homeostatic regulators of cholesterol, and are linked to regulation of broad-affinity xenobiotic transporter activity in non-tumor tissues. We show that LXR ligands confer chemotherapy resistance in TNBC cell lines and xenografts, and that LXRalpha is necessary and sufficient to mediate this resistance. Furthermore, in TNBC patients who had cancer recurrences, LXRalpha and ligands were independent markers of poor prognosis and correlated with P-glycoprotein expression. However, in patients who survived their disease, LXRalpha signaling and P-glycoprotein were decoupled. These data reveal a novel chemotherapy resistance mechanism in this poor prognosis subtype of breast cancer. We conclude that systemic chemotherapy failure in some TNBC patients is caused by co-opting the LXRalpha:P-glycoprotein axis, a pathway highly targetable by therapies that are already used for prevention and treatment of other diseases.

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