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Novel treatment strategies for patients with HER2-positive breast cancer who do not benefit from current targeted therapy drugs.

ABSTRACT: Human epidermal growth factor receptor-2 positive breast cancer (HER2+ BC) is characterized by a high rate of metastasis and drug resistance. The advent of targeted therapy drugs greatly improves the prognosis of HER2+ BC patients. However, drug resistance or severe side effects have limited the application of targeted therapy drugs. To achieve more effective treatment, considerable research has concentrated on strategies to overcome drug resistance. Abemaciclib (CDK4/6 inhibitor), a new antibody-drug conjugate (ADC), src homology 2 (SH2) containing tyrosine phosphatase-1 (SHP-1) and fatty acid synthase (FASN) have been demonstrated to improve drug resistance. In addition, using an effective vector to accurately deliver drugs to tumors has shown good application prospects. Many studies have also found that natural anti-cancer substances produced effective results during in vitro and in vivo anti-HER2+ BC research. This review aimed to summarize the current status of potential clinical drugs that may benefit HER2+ BC patients in the future.

SUBMITTER: Jiang N

PROVIDER: S-EPMC6122384 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Novel treatment strategies for patients with HER2-positive breast cancer who do not benefit from current targeted therapy drugs.

Jiang Nan N Lin Jing-Jing JJ Wang Jun J Zhang Bei-Ning BN Li Ao A Chen Zheng-Yang ZY Guo Song S Li Bin-Bin BB Duan Yu-Zhong YZ Yan Ru-Yi RY Yan Hong-Feng HF Fu Xiao-Yan XY Zhou Jin-Lian JL Yang He-Ming HM Cui Yan Y

Experimental and therapeutic medicine 20180717 3

Human epidermal growth factor receptor-2 positive breast cancer (HER2<sup>+</sup> BC) is characterized by a high rate of metastasis and drug resistance. The advent of targeted therapy drugs greatly improves the prognosis of HER2<sup>+</sup> BC patients. However, drug resistance or severe side effects have limited the application of targeted therapy drugs. To achieve more effective treatment, considerable research has concentrated on strategies to overcome drug resistance. Abemaciclib (CDK4/6 inh ...[more]

PMID: 30186457

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Project description:In one of every four or five cases of breast cancer, the human epidermal growth factor receptor-2 (HER2) gene is overexpressed. These carcinomas are known as HER2-positive. HER2 overexpression is linked to an aggressive phenotype and a lower rate of disease-free and overall survival. Drugs such as trastuzumab, pertuzumab, lapatinib, neratinib, and the more recent afatinib target the deregulation of HER2 expression. Some authors have attributed somatic mutations in HER2, a role in resistance to anti-HER2 therapy as differential regulation of HER2 has been observed among patients. Recently, studies in metastatic ER?+?tumors suggest that some HER2 mutations emerge as a mechanism of acquired resistance to endocrine therapy. In an effort to identify possible biomarkers of the efficacy of anti-HER2 therapy, we here review the known single-nucleotide polymorphisms (SNPs) of the HER2 gene found in HER2-positive breast cancer patients and their relationship with clinical outcomes. Information was recompiled on 11 somatic HER2 SNPs. Seven polymorphisms are located in the tyrosine kinase domain region of the gene contrasting with the low number of mutations found in extracellular and transmembrane areas. HER2-positive patients carrying S310F, S310Y, R678Q, D769H, or I767M mutations seem good candidates for anti-HER2 therapy as they show favorable outcomes and a good response to current pharmacological treatments. Carrying the L755S or D769Y mutation could also confer benefits when receiving neratinib or afatinib. By contrast, patients with mutations L755S, V842I, K753I, or D769Y do not seem to benefit from trastuzumab. Resistance to lapatinib has been reported in patients with L755S, V842I, and K753I. These data suggest that exploring HER2 SNPs in each patient could help individualize anti-HER2 therapies. Advances in our understanding of the genetics of the HER2 gene and its relations with the efficacy of anti-HER2 treatments are needed to improve the outcomes of patients with this aggressive breast cancer.

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Novel treatment strategies for patients with HER2-positive breast cancer who do not benefit from current targeted therapy drugs.

Publications

Novel treatment strategies for patients with HER2-positive breast cancer who do not benefit from current targeted therapy drugs.

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