Abstract
Recent gene profiling studies have identified at least 5 major subtypes of breast cancer, including normal type, luminal A type, luminal B type, human epidermal growth factor receptor (HER)-2 positive type, and basal-like type. Triple-negative breast cancer (TNBC), showing no or low expressions of estrogen receptor (ER), progesterone receptor (PgR), and HER2, considered important clinical biomarkers, accounts for 10% to 20% of all breast cancers. Hormonal therapy and molecular targeted therapy are not indicated for the management of TNBC, resulting in poor outcomes. Because TNBC lacks clear-cut therapeutic targets, effective treatment strategies remain to be established. However, TNBC is known to share similar biologic characteristics with basal-like type breast cancer and is often accompanied by loss of functional BRCA, a gene-modifying enzyme. Breast cancer with BRCA1 or BRCA2 mutations is accompanied by activation of the enzyme poly(ADP-ribose) polymerase (PARP). PARP, a DNA base-excision repair enzyme, is known to play a central role in gene repair, along with BRCA. Because some breast cancers with BRCA1 or BRCA2 mutations are TNBC, the suppression of PARP has attracted attention as a new treatment strategy for TNBC. In this article, we review the clinical characteristics of TNBC, discuss problems in treatment, and briefly summarize the international development status of PARP inhibitors.
Keywords: BRCA, Breast cancer, DNA base-excision repair, PARP, PARP inhibitors, Triple-negative breast cancer
Anti-Cancer Agents in Medicinal Chemistry
Title:Triple-negative Breast Cancer and Poly(ADP-ribose) Polymerase Inhibitors
Volume: 12 Issue: 6
Author(s): Youngjin Park, Ayako Moriyama, Tomoaki Kitahara, Yutaka Yoshida, Tasuku Urita and Ryoji Kato
Affiliation:
Keywords: BRCA, Breast cancer, DNA base-excision repair, PARP, PARP inhibitors, Triple-negative breast cancer
Abstract: Recent gene profiling studies have identified at least 5 major subtypes of breast cancer, including normal type, luminal A type, luminal B type, human epidermal growth factor receptor (HER)-2 positive type, and basal-like type. Triple-negative breast cancer (TNBC), showing no or low expressions of estrogen receptor (ER), progesterone receptor (PgR), and HER2, considered important clinical biomarkers, accounts for 10% to 20% of all breast cancers. Hormonal therapy and molecular targeted therapy are not indicated for the management of TNBC, resulting in poor outcomes. Because TNBC lacks clear-cut therapeutic targets, effective treatment strategies remain to be established. However, TNBC is known to share similar biologic characteristics with basal-like type breast cancer and is often accompanied by loss of functional BRCA, a gene-modifying enzyme. Breast cancer with BRCA1 or BRCA2 mutations is accompanied by activation of the enzyme poly(ADP-ribose) polymerase (PARP). PARP, a DNA base-excision repair enzyme, is known to play a central role in gene repair, along with BRCA. Because some breast cancers with BRCA1 or BRCA2 mutations are TNBC, the suppression of PARP has attracted attention as a new treatment strategy for TNBC. In this article, we review the clinical characteristics of TNBC, discuss problems in treatment, and briefly summarize the international development status of PARP inhibitors.
Export Options
About this article
Cite this article as:
Park Youngjin, Moriyama Ayako, Kitahara Tomoaki, Yoshida Yutaka, Urita Tasuku and Kato Ryoji, Triple-negative Breast Cancer and Poly(ADP-ribose) Polymerase Inhibitors, Anti-Cancer Agents in Medicinal Chemistry 2012; 12 (6) . https://dx.doi.org/10.2174/187152012800617759
DOI https://dx.doi.org/10.2174/187152012800617759 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Muscular Gene Transfer Using Nonviral Vectors
Current Gene Therapy Alternative Splicing: A Promising Target for Pharmaceutical Inhibition of Pathological Angiogenesis?
Current Pharmaceutical Design P-Glycoprotein Mediated Multidrug Resistance Reversal by Phytochemicals: A Review of SAR & Future Perspective for Drug Design
Current Topics in Medicinal Chemistry Endocrine Disruptor Agent Nonyl Phenol Exerts An Estrogen-like Transcriptional Activity on Estrogen Receptor Positive Breast Cancer Cells
Current Medicinal Chemistry Drug-Resistant Epilepsy and Surgery
Current Neuropharmacology Mechanism of Action of Limonene in Tumor Cells: A Systematic Review and Meta-Analysis
Current Pharmaceutical Design Recent Progress and Related Patents on the Applications of Bone Marrow-Derived Stem/Progenitor Cells in Regenerative Medicine and Cancer Therapies
Recent Patents on Regenerative Medicine Rapid Screening of Different Types of Antitumor Compound Groups from Traditional Chinese Medicine by Hollow Fiber Cell Fishing with High Performance Liquid Chromatography
Combinatorial Chemistry & High Throughput Screening Radiolabeled RGD Peptides as Integrin alpha(v)beta3–targeted PET Tracers
Current Medicinal Chemistry Current and Future Prospective of a Versatile Moiety: Imidazole
Current Drug Targets Biologic Agents for Treatment of Rheumatoid Arthritis
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Application of 3-methylene- and 3-(monosubstituted)alkylideneoxindoles in the Synthesis of Heterocyclic Compounds
Current Organic Chemistry Smart Mesoporous Silica Nanocarriers for Antitumoral Therapy
Current Topics in Medicinal Chemistry Autophagy Fails to Alter Withaferin A-Mediated Lethality in Human Breast Cancer Cells
Current Cancer Drug Targets Multimodal Nanomedicine Strategies for Targeting Cancer Cells as well as Cancer Stem Cell Signalling Mechanisms
Mini-Reviews in Medicinal Chemistry Magnetic Iron Oxide Nanoparticles for Tumor-Targeted Therapy
Current Cancer Drug Targets MARK1 is a Novel Target for miR-125a-5p: Implications for Cell Migration in Cervical Tumor Cells
MicroRNA Resveratrol and Clinical Trials: The Crossroad from In Vitro Studies to Human Evidence
Current Pharmaceutical Design Risk Factors for Serious Adverse Effects of Thiopurines in Patients with Crohn’s Disease
Current Drug Safety Meet Our Editorial Board Member
Current Medical Imaging