title: Analysis of different HER-2 mutations in breast cancer progression and drug resistance.
abstract: Studies over the last two decades have identified that amplified human epidermal growth factor receptor (HER-2; c-erbB-2, neu) and its overexpression have been frequently implicated in the carcinogenesis and prognosis in a variety of solid tumours, especially breast cancer. Lots of painstaking efforts were invested on the HER-2 targeted agents, and significantly improved outcome and prolonged the survival of patients. However, some patients classified as 'HER-2-positive' would be still resistant to the anti-HER-2 therapy. Various mechanisms of drug resistance have been illustrated and the alteration of HER-2 was considered as a crucial mechanism. However, systematic researches in regard to the HER-2 mutations and variants are still inadequate. Notably, the alterations of HER-2 play an important role in drug resistance, but also have a potential association with the cancer risk. In this review, we summarize the possible mutations and focus on HER-2 variants' role in breast cancer tumourigenesis. Additionally, the alteration of HER-2, as a potential mechanism of resistance to trastuzumab, is discussed here. We hope that HER-2 related activating mutations could potentially offer more therapeutic opportunities to a broader range of patients than previously classified as HER-2 overexpressed.
authors: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors: Zijia
authors: Z
authors: Sun
authors: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors: Yaqin
authors: Y
authors: Shi
authors: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors: Yan
authors: Y
authors: Shen
authors: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors: Lulu
authors: L
authors: Cao
authors: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors: Wenwen
authors: W
authors: Zhang
authors: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.|Department of Medical Oncology, Jinling Hospital, School of Medicine, Southern Medical University, Guangzhou, China.
authors: Xiaoxiang
authors: X
authors: Guan
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D000077341:Lapatinib; D009154:Mutation; D011799:Quinazolines / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D000068878:Trastuzumab / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: HER-2; HER-2 mutation; breast cancer; cancer risk; resistance; variants