Progress of research on targeted therapy for breast cancer

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1 Δ R A Progress of research on targeted therapy for breast cancer ZENG Jia-jia 1 2 YANG Run-xiang 1 LIU Rong 2Δ 1. Department of Internal Medicine The Third Affiliated Hospital of Kunming Medical University Yunnan Province Tumor Hospital Kunming China 2. Key Laboratory of Animal Models and Human Disease Mechanism Kunming Institute of Zoology Chinese Academy of Sciences Kunming China Abstract Breast cancer is the most common malignancies among women in China. Because of the better effectiveness and less side effects than chemo-and radio-therapies targeted therapy against main signaling pathways of breast carcinogenesis and development has become one of the research focuses in breast cancer research field. In this review we summarized current targeted therapies applied clinically and undergone pre-clinical research against variant molecular subtypes of breast cancer and breast cancer stem cells. Keywords breast cancer targeted therapy breast cancer stem cell 70% ~ 80% estrogen receptor ER 2 ER 12. 2% 9. 6% 1 estrogen estrogen receptor ER progesterone receptor PR 2 human epidermal growth receptor 2 HER2 ER luminal A B HER2 Her2 ER PR HER2 Tamoxifen triple-negative breast cancer TNBC 4 3 E2 ER ER 4 90 aromatase inhibitor AI 1 ER 2015FA027 AI Letrozole 2014J048 E @ 163. com E2 liurong@ mail. kiz. ac. cn E AI 7

2 ER ER % ~ 25% HER / human epidermal growth factor receptor2 HER2 HER2 ER + /HER2 + HER2 Herceptin 1998 HER2 MCF-7 HER2 6 HER2 19 ER ER 7 HER2 ER HER-2 HER2 ER ER 8 HER2 AKT MAPK TAnDEM 2. 2 HER2 III HER1 HER2 HER1 HER2 progression-free survival PFS % % 9 ER + / HER2 + Ⅲ PFS CBR PFS 26% % 3 15% epidermal growth factor receptor EGFR EGFR HER2 Pertuzumab HER2 MAPK ER HER2 HER2 MCF-7 EGFR HER3 EGFR-HER2 HER2 ERK1 /2 11 Gutteridge E 12 Ⅱ HER2 ER PFS vs FDA 53. 6% ER 11. 5% PI3K-Akt-mTOR PI3K-Akt-mTOR 23 T-DM1 MCC 70% PI3K-Akt 13 DM1 Maytansine ER 16 mtor T-DM1 FK FKBP FDA T-DM1 HER2 mtorc-1 TAMRAD ER 3 II 10% ~ 17% 61. 1% vs 42. 1% 14 mtor PI3K mtor TNBC human epidermal growth factor receptor 2 HER Trastuzumab Lapatinib HER2 Ⅲ 21 CLEOPATRA Ⅲ HER2 triple-negative breast cancer TNBC 25 TNBC TNBC TNBC HER ADP- poly ADP-ribose polymerase PARP HER2 PARP DNA PARP EGFR PARP inhibitor PARPI BRCA1 /2 DNA 8

3 PARP TNBC Notch Wnt Hsp27 BCSC I PARPI 38 Olaparib DNA Qiu 39 Notch1 mabs CD44 + / TNBC 26 CD24 low TNBC II PARPI Iniparib PFS overall survival OS vascular endothelial growth factor VEGF 40 Wnt VEGF Wnt1 28 Bevacizumab VEGF-A 41 Wnt Wnt 29 RIBBON-2 42 TNBC 27 heat shock protein 27 Hsp27 ATP Hsp PFS Hsp27 overall remission OR 10% 30 - epithelial-mesenchymal 3. 3 epidermal growth factor receptor EGFR EGFR MAP 32 androgen receptor AR 70% 1 Fan L Strasser-Weippl K Li JJ et al. Breast cancer in China J. 33 TNBC AR 30% AR Wnt /β-catenin JAK /STAT3 MAPK Notch 34 of hypoxia-inducible factor 1 in aromatase inhibitor resistant breast CD44 + /CD24 low CD44 + /CD24 low TNBC Notch γ GSIS Notch GSIS PF transition EMT NF-κB Hsp27 43 Hsp27 AKT VM Cetuximab 5 EGFR EGFR EGFR HER2 TNBC TNBC EGFR TNBC PARP VEGF EGFR EGFR TNBC 3. 4 TNBC TNBC PI3K PTEN INPP4B PI3K PI3K PARP Lancet Oncol e279-e Kazi AA Gilani RA Schech AJ et al. Nonhypoxic regulation and role AR ER /PR Ⅱ cancer J. Breast Cancer Res R15. clinical benefit 3 Harper MJ Walpole AL. A new derivative of triphenylethylene effect rate CBR PFS 35 on implantation and mode of action in rats J. J Reprod Fertil Davies C Godwin Gray J R et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen patient-level meta-analysis of randomised trials J. Lancet Roop RP Ma CX. Endocrine resistance in breast cancer molecular breast cancer stem cell BCSC pathways and rational development of targeted therapies J. Future Oncol Kurokawa H Lenferink AE Simpson JF et al. Inhibition of HER2 / neu erbb-2 and mitogen-activated protein kinases enhances tamoxifen G2 /M action against HER2-overexpressing tamoxifen-resistant breast cancer 37 BCSC cells J. Cancer Res

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