کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8785852 | 1601091 | 2018 | 44 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The role of PARP inhibition in triple-negative breast cancer: Unraveling the wide spectrum of synthetic lethality
ترجمه فارسی عنوان
نقش مهار پارپ در سرطان پستان سه گانه منفی: کشف طیف گسترده ای از مرگ و میر مصنوعی
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
تومور شناسی
چکیده انگلیسی
Triple-negative breast cancer (TNBC) accounts for approximately 15-20% of all breast cancers and is characterized by a lack of immunohistochemical expression of estrogen receptors (ER), progesterone receptors (PR) and HER2. TNBC is associated with poor long-term outcomes compared with other breast cancer subtypes. Many of these tumors are also basal-like cancers which are characterized by an aggressive biological behavior with a distant recurrence peak observed early at 3â¯years following diagnosis. Furthermore, metastatic TNBC bears a dismal prognosis with an average survival of 12â¯months. Although the prevalence of genetic alterations among women with TNBC differs significantly by ethnicity, race and age, BRCA mutations (including both germline mutations and somatic genetic aberrations) are found in up to 20-25% of unselected patients and especially in those of the basal-like immunophenotype. Therefore, defects in the DNA repair pathway could represent a promising therapeutic target for this subgroup of TNBC patients. Poly(ADP-ribose) polymerase (PARP) inhibitors exploit this deficiency through synthetic lethality and have emerged as promising anticancer therapies, especially in BRCA1 or BRCA2 mutation carriers. Several PARP inhibitors are currently being evaluated in the adjuvant, neo-adjuvant, and metastatic setting for the treatment of breast cancer patients with a deficient homologous recombination pathway. In this article, we review the major molecular characteristics of TNBC, the mechanisms of homologous recombination, and the role of PARP inhibition as an emerging therapeutic strategy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Treatment Reviews - Volume 67, June 2018, Pages 34-44
Journal: Cancer Treatment Reviews - Volume 67, June 2018, Pages 34-44
نویسندگان
Marios Papadimitriou, Giannis Mountzios, Christos A. Papadimitriou,