Epigenetic oncogenesis,biomarkers and emerging chemotherapeutics for breast cancer |
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| Affiliation: | 1. Centre for Drug Research, Universiti Sains Malaysia, USM, 11800 Pulau Pinang, Malaysia;2. Department of Chemistry and Industrial Chemistry, Kwara State University, P.M.B., Malete, 1530 Ilorin, Nigeria;1. Structural Genomics Consortium, University of Toronto, Toronto, ON, Canada;2. Department of Pharmacology & Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada;3. Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt;1. Department of Prenatal Screening and Diagnosis Center, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong 226001, China;2. Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong University, Nantong 226001, China;3. Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China;1. Department of Gastroenterology, Peking University Third Hospital, 49 North Garden Road, Beijing, China;2. Beijing Key Laboratory of Helicobacter pylori Infection and Upper Gastrointestinal Diseases, Peking University Third Hospital, 49 North Garden Road, Beijing, China;3. Department of Pathology, School of Basic Medical Science, Peking University Third Hospital, Peking University Health Science Center, 49 North Garden Road, Beijing, China;1. Department of Microbiology, School of Life Sciences, Sikkim University, 6th Mile, Samdur, Gangtok, 737102, Sikkim, India;2. Department of Microbiology, Vidyasagar University, Midnapore, West Bengal 721102, India;1. Departamento de Biología Experimental-Genética, Universidad de Jaén, Paraje de las Lagunillas, s/n, E-23071 Jaén, Spain;2. Instituto Universitario de Investigación en Olivar y Aceites de Oliva, Universidad de Jaén, Paraje de las Lagunillas, s/n, E-23071, Jaén, Spain |
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| Abstract: | Breast cancer remains one of the leading causes of cancer-related deaths globally and the most prominent among females, yet with limited effective therapeutic options. Most of the current medications are challenged by various factors including low efficacy, incessant resistance, immune evasion and frequent recurrence of the disease. Further understanding of the prognosis and identification of plausible therapeutic channels thus requires multimodal approaches. In this review, epigenetics studies of several pathways to BC oncogenesis via the inducement of oncogenic changes on relevant markers have been overviewed. Similarly, the counter-epigenetic mechanisms to reverse such changes as effective therapeutic strategies were surveyed. The epigenetic oncogenesis occurs through several pathways, notably, DNMT-mediated hypermethylation of DNA, dysregulated expression for ERα, HER2/ERBB and PR, histone modification, overexpression of transcription factors including the CDK9-cyclin T1 complex and suppression of tumour suppressor genes. Scientifically, the regulatory reversal of the mechanisms constitutes effective epigenetic approaches for mitigating BC initiation, progression and metastasis. These were exhibited at various experimental levels by classical chemotherapeutic agents including some repurposable drugs, endocrine inhibitors, monoclonal antibodies and miRNAs, natural products, metal complexes and nanoparticles. Dozens of the potential candidates are currently in clinical trials while others are still at preclinical experimental stages showing promising anti-BC efficacy. The review presents a model for a wider understanding of epigenetic oncogenic pathways to BC and reveals plausible channels for reversing the unpleasant changes through epigenetic modifications. It advances the science of therapeutic designs for ameliorating the global burden of BC upon further translational studies. |
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