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通过聚(ADP-核糖)聚合酶-1抑制剂治疗三阴性乳腺癌的方法:最新进展

Therapeutic approach for triple-negative breast Cancer through poly (ADP-ribose) Polymerase-1 inhibitors: Current update.

作者信息

Das Agnidipta, Mandal Sudip Kumar, Arya Swati, Samanta Samir Kumar, Kumar Ashok, Panchpuri Mitali, Abdel-Gawad Hassan, Dwibedi Vagish, Das Niranjan, Bose Sankhadip, Gupta Jeetendra Kumar, Jaitak Vikas, Rath Santosh Kumar

机构信息

Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda 151401, Punjab, India.

Dr. B. C. Roy College of Pharmacy and Allied Health Sciences, Durgapur 713206, West Bengal, India.

出版信息

Bioorg Chem. 2025 May 19;163:108558. doi: 10.1016/j.bioorg.2025.108558.

Abstract

Breast cancer is a dangerous disease that is common worldwide. It comprises 25 % of all women's cancers and 12 % of all new cancer cases diagnosed. Triple-negative breast cancer (TNBC) is a specific subtype of breast cancer that lacks the expression for three targetable biomarkers: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 receptor (HER2). TNBC accounts for 15-20 % of all breast cancers worldwide and is most prevalent in young African-American women, as well as premenopausal women. Unlike other types of breast cancer, TNBC has limited treatment options. Mutations in the Breast Cancer type 1 and type 2 genes (BRCA1/2) are associated with TNBC. However, researchers are investigating new approaches to treating this subtype. One promising area of research is focused on Poly (ADP-Ribose) Polymerases (PARPs), a family of enzymes involved in DNA repair. Inhibition of PARP-1 can led to the loss of DNA repair via BRCA-dependent mechanisms. PARP-1 inhibitors such as Olaparib, Rucaparib, Niraparib, and Talazoparib have shown promise in treating various types of cancer. These inhibitors are being tested both as monotherapy and in combination with other therapies, such as cytotoxic therapy or radiotherapy. This review article focuses on exploring the significance of PARP-1 inhibitors for TNBC. It delves into the mechanism of action and discusses current and future perspectives for using these inhibitors to treat TNBC.

摘要

乳腺癌是一种在全球范围内常见的危险疾病。它占所有女性癌症的25%,以及所有新诊断癌症病例的12%。三阴性乳腺癌(TNBC)是乳腺癌的一种特定亚型,缺乏三种可靶向生物标志物的表达:雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子2受体(HER2)。TNBC在全球所有乳腺癌中占15%-20%,在年轻的非裔美国女性以及绝经前女性中最为普遍。与其他类型的乳腺癌不同,TNBC的治疗选择有限。乳腺癌1型和2型基因(BRCA1/2)的突变与TNBC有关。然而,研究人员正在研究治疗这种亚型的新方法。一个有前景的研究领域集中在聚(ADP-核糖)聚合酶(PARP)上,这是一类参与DNA修复的酶。抑制PARP-1可导致通过BRCA依赖机制的DNA修复丧失。PARP-1抑制剂如奥拉帕尼、鲁卡帕尼、尼拉帕尼和他拉唑帕尼在治疗各种类型癌症方面已显示出前景。这些抑制剂正在作为单一疗法以及与其他疗法(如细胞毒性疗法或放射疗法)联合进行测试。这篇综述文章重点探讨PARP-1抑制剂对TNBC的重要性。它深入研究了作用机制,并讨论了使用这些抑制剂治疗TNBC的当前和未来前景。

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