Genomic instability in breast and ovarian cancers: translation into clinical predictive biomarkers.
Summary of "Genomic instability in breast and ovarian cancers: translation into clinical predictive biomarkers."
Breast and ovarian cancer are among the most common malignancies diagnosed in women worldwide. Together, they account for the majority of cancer-related deaths in women. These cancer types share a number of features, including their association with hereditary cancer syndromes caused by heterozygous germline mutations in BRCA1 or BRCA2. BRCA-associated breast and ovarian cancers are hallmarked by genomic instability and high sensitivity to DNA double-strand break (DSB) inducing agents due to loss of error-free DSB repair via homologous recombination (HR). Recently, poly(ADP-ribose) polymerase inhibitors, a new class of drugs that selectively target HR-deficient tumor cells, have been shown to be highly active in BRCA-associated breast and ovarian cancers. This finding has renewed interest in hallmarks of HR deficiency and the use of other DSB-inducing agents, such as platinum salts or bifunctional alkylators, in breast and ovarian cancer patients. In this review we discuss the similarities between breast and ovarian cancer, the hallmarks of genomic instability in BRCA-mutated and BRCA-like breast and ovarian cancers, and the efforts to search for predictive markers of HR deficiency in order to individualize therapy in breast and ovarian cancer.
Affiliation
Division of Molecular Biology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands, m.vollebergh@nki.nl.
Journal Details
This article was published in the following journal.
Name: Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21922196
- DOI: http://dx.doi.org/10.1007/s00018-011-0809-0
Medical and Biotech [MESH] Definitions
Neoplasms, Ductal, Lobular, And Medullary
Neoplasms, usually carcinoma, located within the center of an organ or within small lobes, and in the case of the breast, intraductally. The emphasis of the name is on the location of the neoplastic tissue rather than on its histological type. Most cancers of this type are located in the breast.
Genomic Instability
An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.
Li-fraumeni Syndrome
Rare autosomal dominant syndrome characterized by mesenchymal and epithelial neoplasms at multiple sites. MUTATION of the p53 tumor suppressor gene, a component of the DNA DAMAGE response pathway, apparently predisposes family members who inherit it to develop certain cancers. The spectrum of cancers in the syndrome was shown to include, in addition to BREAST CANCER and soft tissue sarcomas (SARCOMA); BRAIN TUMORS; OSTEOSARCOMA; LEUKEMIA; and ADRENOCORTICAL CARCINOMA.
Breast Cyst
A fluid-filled closed cavity or sac that is lined by an EPITHELIUM and found in the BREAST. It may appear as a single large cyst in one breast, multifocal, or bilateral in FIBROCYSTIC BREAST DISEASE.
Microsatellite Instability
The occurrence of highly polymorphic mono- and dinucleotide MICROSATELLITE REPEATS in somatic cells. It is a form of genome instability associated with defects in DNA MISMATCH REPAIR.
PubMed Articles
Genomic instability in pre-neoplastic colonic lesions.
Genomic instability is a characteristic of most cancers and it is argued that genomic instability is a driving force for tumorigenesis. Data herein demonstrate that genomic instability, as evidenced b...
The familial aggregation of breast cancer has been well-described with approximately 25 % of breast cancers attributable to inherited mutations in currently known breast cancer susceptibility genes....
Receptors luteinizing hormone-releasing hormone (LHRH) are expressed in about 80 % of human endometrial and ovarian cancers and account for more than 50 % of breast cancers including triple negative...
The detection and implication of genome instability in cancer.
Genomic instability is a hallmark of cancer that leads to an increase in genetic alterations, thus enabling the acquisition of additional capabilities required for tumorigenesis and progression. Subst...
Platinum Resistance in Breast and Ovarian Cancer Cell Lines.
ABSTRACT: Breast and ovarian cancers are among the 10 leading cancer types in females with mortalities of 15% and 6%, respectively. Despite tremendous efforts to conquer malignant diseases, the war on...
Clinical Trials
The purpose of this study is to evaluate the anti-tumor activity of 852A when used to treat metastatic breast, ovarian, endometrial or cervical cancer not responding to standard treatment.
NB1011 Administered by Continuous Infusion in Cancers That Overexpress Thymidylate Synthase (TS)
The purpose of this trial is to assess the tolerability and safety of NB1011 in the treatment of patients with cancers that overexpress TS, such as ovarian, gastrointestinal, colorectal, b...
Screening for Gynecologic Cancers in Hereditary Nonpolyposis Colorectal Cancer (HNPCC) Patients
Among women with HNPCC, this study will assess: 1. Knowledge of screening recommendations for endometrial and ovarian cancers. 2. Perceived risk and cancer worries regarding endometr...
Despite intensive research efforts, there are still no simple and effective screening tools to detect early lung cancer. The majority of newly diagnosed patients have higher stage, often...
Attitudes About Childbearing And Fertility With Inherited Breast And Ovarian Cancer Syndromes (HBOC)
Objectives: - To evaluate the attitudes and opinions of women undergoing genetic counseling for hereditary breast and ovarian cancer syndrome, both before and after testing, in regards to...
