Abstract：
:Breast cancer (BC) cell de-sensitization to Tamoxifen (TAM) or other selective estrogen receptor (ER) modulators (SERM) is a complex process associated with BC heterogeneity and the transformation of ER signalling. The most influential resistance-related mechanisms include modifications in ER expression and gene regulation patterns. During TAM/SERM treatment, epigenetic mechanisms can effectively silence ER expression and facilitate the development of endocrine resistance. ER status is efficiently regulated by specific epigenetic tools including hypermethylation of CpG islands within ER promoters, increased histone deacetylase activity in the ER promoter, and/or translational repression by miRNAs. Over-methylation of the ER α gene (ESR1) promoter by DNA methyltransferases was associated with poor prognosis and indicated the development of resistance. Moreover, BC progression and spreading were marked by transformed chromatin remodelling, post-translational histone modifications, and expression of specific miRNAs and/or long non-coding RNAs. Therefore, targeted inhibition of histone acetyltransferases (e.g. MYST3), deacetylases (e.g. HDAC1), and/or demethylases (e.g. lysine-specific demethylase LSD1) was shown to recover and increase BC sensitivity to anti-estrogens. Indicated as a powerful molecular instrument, the administration of epigenetic drugs can regain ER expression along with the activation of tumour suppressor genes, which can in turn prevent selection of resistant cells and cancer stem cell survival. This review examines recent advances in the epigenetic regulation of endocrine drug resistance and evaluates novel anti-resistance strategies. Underlying molecular mechanisms of epigenetic regulation will be discussed, emphasising the utilization of epigenetic enzymes and their inhibitors to re-program irresponsive BCs.
journal_name
Semin Cancer Bioljournal_title
Seminars in cancer biologyauthors
Sukocheva OA,Lukina E,Friedemann M,Menschikowski M,Hagelgans A,Aliev Gdoi
10.1016/j.semcancer.2020.12.004subject
Has Abstractpub_date
2020-12-07 00:00:00eissn
1044-579Xissn
1096-3650pii
S1044-579X(20)30263-7pub_type
杂志文章abstract：:The role of F-box proteins in pancreatic tumorigenesis is emerging owing to their pivotal and indispensable roles in cell differentiation, cell cycle regulation and proliferation. In this review, we will focus on β-TrCP (β-transducin repeat-containing protein) and two other prototypical mammalian F-box proteins, Fbxw7...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2015.09.004
更新日期：2016-02-01 00:00:00
abstract：:The understanding of the relationship between epigenetic alterations, their effects on gene expression and the knowledge that these epigenetic alterations are reversible, have opened up new therapeutic pathways for treating various diseases, including cancer. This has led the research for a better understanding of the...
journal_title：Seminars in cancer biology
pub_type： 杂志文章
doi：10.1016/j.semcancer.2020.12.018
更新日期：2021-01-06 00:00:00
abstract：:Ubiquitination plays a key role in regulating the tumour suppressor p53. It targets p53 for degradation by the 26S proteasome. The ubiquitin pathway also regulates the activity and localisation of p53. Ubiquitination requires ubiquitin-activating and -conjugating enzymes and ubiquitin ligases. In addition, ubiquitinat...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2009.10.004
更新日期：2010-02-01 00:00:00
abstract：:The ubiquitin-proteasome system (UPS) plays a central role in the degradation of cellular proteins. Targeting protein degradation has been validated as an effective strategy for cancer therapy since 2003. Several components of the UPS have been validated as potential anticancer targets, including 20S proteasomes, 19S ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.12.013
更新日期：2019-12-26 00:00:00
abstract：:Tumor-stromal interactions induce expression of matrix metalloproteinases and serine proteases and, as shown recently, the cysteine protease cathepsin B. We speculate that such interactions upregulate the transcription factor Ets1, resulting in increased cathepsin B expression. This would be consistent with the observ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2004.08.001
更新日期：2005-04-01 00:00:00
abstract：:Cancer-testis antigens (CTAs) are considered as unique and promising cancer biomarkers and targets for cancer therapy. CTAs are multifunctional protein group with specific expression patterns in normal embryonic and adult cells and various types of cancer cells. CTAs are involved in regulating of the basic cellular pr...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2018.08.006
更新日期：2018-12-01 00:00:00
abstract：:High-throughput molecular profiling of tumors is a fundamental aspect of precision oncology, enabling the identification of genomic alterations that can be targeted therapeutically. In this context, a patient is matched to a specific drug or therapy based on the tumor's underlying genetic driver events rather than the...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2020.12.020
更新日期：2021-01-18 00:00:00
abstract：:Recently, work on the mechanism of action of the von Hippel-Lindau tumour suppressor protein (pVHL) and studies on hypoxic gene regulation have converged, providing insights into both cellular oxygen sensing and cancer pathogenesis. pVHL is the recognition component of the E3-ubiquitin ligase complex involved in the d...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/s1044-579x(02)00103-7
更新日期：2003-02-01 00:00:00
abstract：:Natural killer (NK) cells are important mediators of resistance against tumor growth and metastasis. NK cell reactivity is regulated by a balance of signals from activating and inhibitory receptors. While reactivity against tumor cells is beneficial, it is essential that NK cells do not attack normal tissue. The disti...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2006.07.013
更新日期：2006-10-01 00:00:00
abstract：:Dysfunction of the TP53 (p53) gene occurs in most if not all human malignancies. Two principal mechanisms are responsible for this dysfunction; mutation and downregulation of wild-type p53 mediated by MDM2/MDM4. Because of its almost universal inactivation in malignancy, p53 is a highly attractive target for the devel...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2020.07.005
更新日期：2020-07-31 00:00:00
abstract：:The Signal Transducer and Activator of Transcription (STAT) family of proteins consists of transcription factors that play a complex and essential role in the regulation of physiologic cell processes, such as proliferation, differentiation, apoptosis and angiogenesis, and serves to organize the epigenetic landscape of...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.10.002
更新日期：2020-02-01 00:00:00
abstract：:Altering energy metabolism to meet the uncontrolled proliferation and metastasis has emerged as one of the most significant hallmarks in tumors. However, the detailed molecular mechanisms and regulatory actions underlying have not been fully elucidated. As a family of NAD+ dependent protein modifying enzymes, sirtuins...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2018.11.003
更新日期：2019-08-01 00:00:00
abstract：:Gene vectors with an untargeted insertion profile have been explored in preclinical models and clinical trials for the transfer of potentially therapeutic genetic information into somatic cells that have a high replicative potential. The gene-modified cell population can be viewed as a genetic mosaic whose complexity ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2010.06.003
更新日期：2010-08-01 00:00:00
abstract：:Nucleotide sequence analysis at five distinct loci across the 140, 000 bp genomes of more than 60 KSHV samples from KS and PEL tumors from North America, Africa, the Middle East, Asia and the Pacific revealed that they cluster into four major subtypes (A, B, C and D) that have close associations with the geographic an...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.1998.0116
更新日期：1999-06-01 00:00:00
abstract：:The cysteine proteinase cathepsin B has been implicated in the progression of tumors from a premalignant to a malignant state. Activity of cathepsin B has been shown to be elevated in parallel with malignancy or metastatic potential of human and rodent tumors. These increases in cathepsin B activity correspond in part...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1990-04-01 00:00:00
abstract：:Intellectual property documents (patents and their published applications) are not only collections of legal exclusivity claims but also repositories of scientific and technical information, even though they are not peer reviewed. We have identified and analyzed international disclosures concerning drug repurposing fo...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.09.010
更新日期：2019-09-20 00:00:00
abstract：:Epigenetic alterations of the genome such as DNA promoter methylation and chromatin remodeling play an important role in tumorigenesis. Recent findings indicate epigenetic modifications as key factors in breast carcinogenesis. These modifications are quite appealing as targets for preventative care and therapeutics be...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2009.02.007
更新日期：2009-06-01 00:00:00
abstract：:Human bladder carcinogenesis stands as a paradigm for research on the molecular genetic mechanisms of chemical carcinogenesis. The pathogenesis of bladder cancer is multistage with a typical onset later in life. Epidemiological studies associate occupational exposure to aromatic amines with increased bladder cancer ri...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1993-06-01 00:00:00
abstract：:The key molecule for normal B cells is the surface Ig (sIg) of the B-cell receptor, which influences cell behaviour, even after neoplastic transformation. During B-cell maturation, sIg accumulates somatic mutations in the Ig variable region (V) genes and tumours retain these patterns, thereby revealing the point of di...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2010.08.004
更新日期：2010-12-01 00:00:00
abstract：:Large-scale sequencing methodologies have helped us identify numerous genomic alterations and we have started to scratch the surface of many new targets for treatment of cancer and the associated predictive biomarkers. TRAIL (TNF-related apoptosis-inducing ligand) is a highly appreciated anti-cancer molecule because o...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.01.007
更新日期：2019-10-01 00:00:00
abstract：:Disseminated tumor cells are present in many patients at diagnosis. At a time when the disseminated disease becomes prominent, patients have already been treated with many cycles of therapy to which their metastases were also exposed. These metastases have genetically evolved from primary tumors. Furthermore, their in...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2012.03.005
更新日期：2012-06-01 00:00:00
abstract：:Maintenance and accurate propagation of the genetic material are key features for physiological development and wellbeing. The replication licensing machinery is crucial for replication precision as it ensures that replication takes place once per cell cycle. Thus, the expression status of the components comprising th...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2015.12.002
更新日期：2016-06-01 00:00:00
abstract：:Cells adhere to one another and/or to matrices that surround them. Regulation of cell-cell (intercellular) and cell-matrix adhesion is tightly controlled in normal cells, however, defects in cell adhesion are common in the majority of human cancers. Multilateral communication among tumor cells with the extracellular m...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2010.05.002
更新日期：2010-06-01 00:00:00
abstract：:Investigations across a range of disciplines over the past decade have brought the study of cell motility and its role in invasion to an exciting threshold. The biophysical forces proximally involved in generating cell locomotion, as well as the underlying signaling and genomic regulatory processes, are gradually beco...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.2000.0362
更新日期：2001-04-01 00:00:00
abstract：:Epidemiological studies implicate steroid hormones as important factors in the development of neoplasia, and hormonal manipulation constitutes an important treatment arm in cancer therapy. Recent studies demonstrate a key role for nuclear receptor proteins in the expression of genes encoding the cytochrome P450 enzyme...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1994-10-01 00:00:00
abstract：:Gynaecological carcinosarcomas are the most lethal gynaecological malignancies that are often highly resistant to standard chemotherapy. They are composed of both carcinomatous and sarcomatous components and are associated with high rates of metastatic disease. Due to their rarity, molecular studies have been carried ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.10.006
更新日期：2020-04-01 00:00:00
abstract：:Although much of cancer research relies on Nowell's clonal evolution hypothesis as a conceptual framework, large gaps remain in understanding how tumors develop. The multistage skin cancer model in mice provides continuing insight on fundamental aspects of tumor evolution. In this model, mutation of the oncogene Hras ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2005.06.003
更新日期：2005-12-01 00:00:00
abstract：:System approaches in biology have a long history. We focus here on the thinking of Paul A. Weiss and Ludwig von Bertalanffy, who contributed a great deal towards making the system concept operable in biology in the early 20th century. To them, considering whole living systems, which includes their organisation or orde...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2011.05.001
更新日期：2011-06-01 00:00:00
abstract：:About a century ago Otto Warburg observed that tumor cells exhibited increased glycolysis despite the presence of oxygen and stated this metabolic shift to glycolysis as the origin of cancer cell. In the meantime it has become clear, that the altered glucose metabolism is only one piece of the tumor metabolome puzzle....
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2012.02.009
更新日期：2012-08-01 00:00:00
abstract：:Viability is a fundamental determinant of all cellular functions, and regulation of cell viability is important in shaping tissue differentiation and organism development. The genes in the bcl-2 family can profoundly influence cell viability. In addition to bcl-2, cellular genes in this family include bcl-x, bax, mcl-...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.1995.0005
更新日期：1995-02-01 00:00:00
