Histone Deacetylases as New Therapeutic Targets in Triple-negative Breast Cancer: Progress and Promises

doi:10.21873/cgp.20041

Cited by 49 publications

(30 citation statements)

References 157 publications

(207 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…According to functional criteria, histone deacetylases (HDAC) can be classified in four classes, which can be divided into two groups, the NADdependent class III and the Zn 2+ -dependent classes of I, II and IV. These classes include a) hydroxamates, b) benzamides c) cyclic peptides and d) aliphatic acids (51). HDAC inhibitors (HDACI) affect a wider spectrum of cellular functions in cancer cells, such as cell proliferation, cell death, gene expression and cell migration (52).…”

Section: Entry 1) Patients Received Treatment With 4-mentioning

confidence: 99%

Triple-Negative Breast Cancer: The Progress of Targeted Therapies and Future Tendencies

et al. 2019

View full text Add to dashboard Cite

Triple-negative breast cancer (TNBC) is characterized by a lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) and unfortunately is not associated with good prognosis. Treatment of breast cancer mainly depends on chemotherapy, due to the lack of specifically approved targeted therapies for TNBC. It is of paramount importance to find new therapeutic approaches, as resistance to chemotherapy frequently occurs. Herein, we present clinical studies published within the last five years, in order to reveal possible targeted therapies against TNBC. We aimed to discuss factors against TNBC, such as tyrosine kinase inhibitors, anti-androgens, poly ADP-ribose polymerase-1 (PARP-1) inhibitors, anti-angiogenic factors, immune checkpoints and histone deacetylase inhibitors (HDACI). Furthermore, the PI3K/AKT/mTOR pathway seems to be a promising field for the development of new anti-TNBC targeted therapies. Data from 18 clinical trials with patients suffering from TNBC were summarized and presented descriptively. Breast cancer is one of the most common cancers in females, comprising heterogeneous tumors with a variety of biological features, clinical course, prognosis and response to therapy (1, 2). In 2017, triple-negative breast cancer (TNBC) accounted for about 15% of all the new cases of breast cancer in the United States (3-7). Many different epidemiological studies have revealed that TNBC was more likely to arise among females characterized by early menarche, higher waist to hip ratio, higher parity, shorter duration of breast feeding, higher body mass index, and was more common among pre-menopausal patients (8). TNBC is a disease defined by the absence of human epidermal growth factor receptor 2 (HER2) and hormone receptors (HR), specifically the progesterone (PR) and the estrogen receptor (ER) (9) (Figure 1). There are at least 6 different subtypes, which demonstrate different biological behavior, including the basal-like 1 and 2 (BL-1 and BL-2), mesenchymal (M), mesenchymal stem-like (MSL), immunomodulatory (IM), luminal androgen receptor (LAR) and unstable subtype (7, 10).

show abstract

Section: Entry 1) Patients Received Treatment With 4-mentioning

confidence: 99%

Triple-Negative Breast Cancer: The Progress of Targeted Therapies and Future Tendencies

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Significantly, both CCT and HDAC complexes are potential druggable targets for cancer therapy. The HDAC inhibitor SAHA is currently used for treating triple negative breast cancer TNBC patients 52 , and the drug CT20p, which targets the CCT complex, is currently being investigated for its therapeutic potential for lung and breast cancer treatment 53 , 54 . Based on our results, it is conceivable that investigating therapeutic approaches that target both HDAC and CCT complexes together could be worthwhile.…”

Section: Discussionmentioning

confidence: 99%

Differential HDAC1/2 network analysis reveals a role for prefoldin/CCT in HDAC1/2 complex assembly

Banks

Miah

Adams

et al. 2018

Sci Rep

View full text Add to dashboard Cite

HDAC1 and HDAC2 are components of several corepressor complexes (NuRD, Sin3, CoREST and MiDAC) that regulate transcription by deacetylating histones resulting in a more compact chromatin environment. This limits access of transcriptional machinery to genes and silences transcription. While using an AP-MS approach to map HDAC1/2 protein interaction networks, we noticed that N-terminally tagged versions of HDAC1 and HDAC2 did not assemble into HDAC corepressor complexes as expected, but instead appeared to be stalled with components of the prefoldin-CCT chaperonin pathway. These N-terminally tagged HDACs were also catalytically inactive. In contrast to the N-terminally tagged HDACs, C-terminally tagged HDAC1 and HDAC2 captured complete histone deacetylase complexes and the purified proteins had deacetylation activity that could be inhibited by SAHA (Vorinostat), a Class I/II HDAC inhibitor. This tag-mediated reprogramming of the HDAC1/2 protein interaction network suggests a mechanism whereby HDAC1 is first loaded into the CCT complex by prefoldin to complete folding, and then assembled into active, functional HDAC complexes. Imaging revealed that the prefoldin subunit VBP1 colocalises with nuclear HDAC1, suggesting that delivery of HDAC1 to the CCT complex happens in the nucleus.

show abstract

“…Crucial preclinical trials on HDAC inhibitors (panobinostat, vorinostat, and entinostat) exert an anti-proliferative effect on TNBC cells and control tumor growth by multiple mechanisms of action, including apoptosis and regulation of the epithelial to mesenchymal transition (EMT). HDAC inhibitors such as suberoylanilidehydroxamic acid (SAHA), sodium butyrate, mocetinostat, panobinostat, entinostat, YCW1 and N-(2-hydroxyphenyl)-2-propylpentanamide have shown promising therapeutic outcomes against TNBC, especially when they are used in combination with other anticancer agents [29,30].…”

Section: Discussionmentioning

confidence: 99%

Trichostatin A inhibits proliferation of triple negative breast cancer cells by inducing cell cycle arrest and apoptosis

Song

et al. 2018

neo

View full text Add to dashboard Cite

Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with poor outcome. Because of lacking therapeutic targets, chemotherapy is the main treatment option for patients with TNBC. Overexpression of HDACs correlates with tumorigenesis, highlighting the potential of HDACs as therapeutic targets for TNBC. Here we demonstrate that trichostatin A (TSA, a HDAC inhibitor) selectively inhibits the proliferation of TNBC cell lines HCC1806 and HCC38 rather than a normal breast cell line MCF10A. The inhibition of TNBC by TSA is via its roles in inducing cell cycle arrest and apoptosis. TSA treatment leads to decreased expression of CYCLIN D1, CDK4, CDK6 and BCL-XL, but increased P21 expression. Moreover, combination of TSA with doxorubicin has synergistic effects on inhibiting proliferation of HCC1806 and HCC38 cells. Our studies identified a promising epigenetic-based therapeutic strategy that may be implemented in the therapy of fatal human breast cancer.

show abstract

Histone Deacetylases as New Therapeutic Targets in Triple-negative Breast Cancer: Progress and Promises

Abstract: Abstract. Triple-negative breast cancer (TNBC) lacks expression of estrogen receptor (ER), progesterone receptor (PR) and HER2 gene. It comprises approximately 15-20% of breast cancers (BCs

Cited by 49 publications

References 157 publications

Triple-Negative Breast Cancer: The Progress of Targeted Therapies and Future Tendencies

Triple-Negative Breast Cancer: The Progress of Targeted Therapies and Future Tendencies

Differential HDAC1/2 network analysis reveals a role for prefoldin/CCT in HDAC1/2 complex assembly

Trichostatin A inhibits proliferation of triple negative breast cancer cells by inducing cell cycle arrest and apoptosis

Contact Info

Product

Resources

About