BRCA1, PARP, and 53BP1: conditional synthetic lethality and synthetic viability
نویسندگان
چکیده
منابع مشابه
BRCA1, PARP, and 53BP1: conditional synthetic lethality and synthetic viability.
BRCA1 plays a critical role in the regulation of homologous recombination (HR)-mediated DNA double-strand break repair. BRCA1-deficient cancers have evolved to tolerate loss of BRCA1 function. This renders them vulnerable to agents, such as PARP inhibitors, that are conditionally 'synthetic lethal' with their underlying repair defect. Recent studies demonstrate that BRCA1-deficient cells may ac...
متن کاملPredictors and Modulators of Synthetic Lethality: An Update on PARP Inhibitors and Personalized Medicine
Poly(ADP-ribose) polymerase (PARP) inhibitors have proven to be successful agents in inducing synthetic lethality in several malignancies. Several PARP inhibitors have reached clinical trial testing for treatment in different cancers, and, recently, Olaparib (AZD2281) has gained both United States Food and Drug Administration (USFDA) and the European Commission (EC) approval for use in BRCA-mut...
متن کاملSynthetic lethality of PARP and NAMPT inhibition in triple-negative breast cancer cells
PARP inhibitors have been proposed as a potential targeted therapy for patients with triple-negative (ER-, PR-, HER2-negative) breast cancers. However, it is as yet unclear as to whether single agent or combination therapy using PARP inhibitors would be most beneficial. To better understand the mechanisms that determine the response to PARP inhibitors, we investigated whether enzymes involved i...
متن کاملEnhancing synthetic lethality of PARP-inhibitor and cisplatin in BRCA-proficient tumour cells with hyperthermia
BACKGROUND Poly-(ADP-ribose)-polymerase1 (PARP1) is involved in repair of DNA single strand breaks. PARP1-inhibitors (PARP1-i) cause an accumulation of DNA double strand breaks, which are generally repaired by homologous recombination (HR). Therefore, cancer cells harboring HR deficiencies are exceptionally sensitive to PARP1-i. For patients with HR-proficient tumors, HR can be temporarily inhi...
متن کاملProtease Addiction and Synthetic Lethality in Cancer
The "oncogene addiction" concept refers to the dependence of cancer cells on the function of the oncogenes responsible for their transformed phenotype, while the term "non-oncogene addiction" has been introduced to define the exacerbated necessity of the normal function of non-mutated genes. In this Perspective, we focus on the importance of proteolytic enzymes to maintain the viability of canc...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Journal of Molecular Cell Biology
سال: 2011
ISSN: 1674-2788
DOI: 10.1093/jmcb/mjq055