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Review
. 2022 Mar 4:12:828438.
doi: 10.3389/fonc.2022.828438. eCollection 2022.

New Advances in Targeted Therapy of HER2-Negative Breast Cancer

Junsha An  1 , Cheng Peng  2 , Xiaofang Xie  2 , Fu Peng  1   2
Affiliations
Review

New Advances in Targeted Therapy of HER2-Negative Breast Cancer

Junsha An et al. Front Oncol. .

Abstract

Breast cancer has an extremely high incidence in women, and its morbidity and mortality rank first among female tumors. With the increasing development of molecular biology and genomics, molecular targeted therapy has become one of the most active areas in breast cancer treatment research and has also achieved remarkable achievements. However, molecular targeted therapy is mainly aimed at HER2-positive breast cancer and has not yet achieved satisfactory curative effect on HER2-negative breast cancer. This article describes the potential targets that may be used for breast cancer treatment from the aspects of PI3K/AKT signaling pathway, DDR, angiogenesis, the cell cycle, breast cancer stem cells, etc., and explores possible inhibitors for the treatment of HER2-negative breast cancer, such as PI3K inhibitors, AKT inhibitors and m-TOR inhibitors that inhibit the PI3K/AKT signaling pathway, small molecule tyrosine kinase inhibitors that restrain angiogenesis, CDK inhibitors, aurora kinase inhibitors and HDAC inhibitors that block cell cycle, as well as the drugs targeting breast cancer stem cells which have been a hit, aiming to provide a new idea and strategy for the treatment of HER2-negative breast cancer.

Keywords: HER2-negative; breast cancer; inhibitors; multiple targets; targeted therapy.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
PI3K/AKT pathway targets and inhibitors.
Figure 2
Figure 2
DNA damage response and repair pathways.
Figure 3
Figure 3
Cell cycle signaling pathways and inhibitors.
See this image and copyright information in PMC

References

    1. Heer E, Harper A, Escandor N, Sung H, McCormack V, Fidler-Benaoudia MM. Global Burden and Trends in Premenopausal and Postmenopausal Breast Cancer: A Population-Based Study. Lancet Glob Health (2020) 8(8):e1027–37. doi: 10.1016/S2214-109X(20)30215-1 - DOI - PubMed
    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries [Published Correction Appears in CA Cancer J Clin. 2020 Jul;70(4):313]. CA Cancer J Clin (2018) 68(6):394–424. doi: 10.3322/caac.21492 - DOI - PubMed
    1. Yersal O, Barutca S. Biological Subtypes of Breast Cancer: Prognostic and Therapeutic Implications. World J Clin Oncol (2014) 5(3):412–24. doi: 10.5306/wjco.v5.i3.412 - DOI - PMC - PubMed
    1. Xuhong JC, Qi XW, Zhang Y, Jiang J. Mechanism, Safety and Efficacy of Three Tyrosine Kinase Inhibitors Lapatinib, Neratinib and Pyrotinib in HER2-Positive Breast Cancer. Am J Cancer Res (2019) 9(10):2103–19. - PMC - PubMed
    1. Fisusi FA, Akala EO. Drug Combinations in Breast Cancer Therapy. Pharm Nanotechnol (2019) 7(1):3–23. doi: 10.2174/2211738507666190122111224 - DOI - PMC - PubMed