乳腺癌内分泌治疗耐药机制的研究进展
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摘要
乳腺癌是中国女性常见的恶性肿瘤之一,严重威胁着人们的健康和生命。70%～80%乳腺癌为激素受体阳性,目前针对这一类型乳腺癌的主要治疗手段为内分泌治疗。近几十年来内分泌治疗领域的新药不断问世并逐渐应用于临床,虽然对提高患者的疗效和延长生存时间方面带来希望,但内分泌治疗的耐药现状也受到人们重视。本文将对乳腺癌内分泌治疗的耐药机制和最新的研究结果进行综述,以期为乳腺癌内分泌治疗耐药的早期监测和干预提供新的思路。
In China breast cancer is one of the common cancers for female, which seriously threatens people's health and life. Seventy to eighty percent of breast cancers are estrogen receptor(ER)-positive tumors. Endocrine therapy is the main strategy for ER-positive breast cancer. Novel endocrine drugs, which have brought hopes to improve the therapeutic effect and prolong the overall survival of patients, have been created and used for patients with ER-positive breast cancer in the recent decades. However, the resistance to endocrine therapy has gradually emerged to be a severe problem. In order to provide new ideas targeting endocrine resistance for early prediction and treatment of ER-positive breast cancer, we combined the current theory and mechanism of endocrine resistance,as well as the latest published research results in this review.
In China breast cancer is one of the common cancers for female, which seriously threatens people's health and life. Seventy to eighty percent of breast cancers are estrogen receptor(ER)-positive tumors. Endocrine therapy is the main strategy for ER-positive breast cancer. Novel endocrine drugs, which have brought hopes to improve the therapeutic effect and prolong the overall survival of patients, have been created and used for patients with ER-positive breast cancer in the recent decades. However, the resistance to endocrine therapy has gradually emerged to be a severe problem. In order to provide new ideas targeting endocrine resistance for early prediction and treatment of ER-positive breast cancer, we combined the current theory and mechanism of endocrine resistance,as well as the latest published research results in this review.
引文
[1]Fan W,Chang J,Fu P.Endocrine therapy resistance in breast cancer:current status,possible mechanisms and overcoming strategies[J].Future Med Chem,2015,7(12):1511-1519.
[2]Rugo HS,Rumble RB,Macrae E,et al.Endocrine therapy for hormone receptor-positive metastatic breast cancer:American society of clinical oncology guideline[J].J Clin Oncol,2016,34(25):3069-3103.
[3]García-Becerra R,Santos N,Díaz L,et al.Mechanisms of resistance to endocrine therapy in breast cancer:focus on signaling pathways,miRNAs and genetically based resistance[J].Int J Mol Sci,2012,14(1):108-145.
[4]Chang M.Tamoxifen resistance in breast cancer[J].Biomol Ther(Seoul),2012,20(3):256-267.
[5]Ojo D,Wei F,Liu Y,et al.Factors promoting tamoxifen resistance in breast cancer via stimulating breast cancer stem cell expansion[J].Curr Med Chem,2015,22(19):2360-2374.
[6]Yin L,Pan X,Zhang XT,et al.Downregulation of ER-α36 expression sensitizes HER-2 overexpressing breast cancer cells to tamoxifen[J].Am J Cancer Res,2015,5(2):530-544.
[7]Osborne CK,Bardou V,Hopp TA,et al.Role of the estrogen receptor coactivator AIB1(SRC-3)and HER-2/neu in tamoxifen resistance in breast cancer[J].J Natl Cancer Inst,2003,95(5):353-361.
[8]Shibata T,Watari K,Izumi H,et al.Breast cancer resistance to antiestrogens is enhanced by increased ER degradation and ERBB2 expression[J].Cancer Res,2017,77(2):545-556.
[9]Shen Y,Zhong J,Liu J,et al.Protein arginine N-methyltransferase 2reverses tamoxifen resistance in breast cancer cells through suppression of ER-α36[J].Oncol Rep,2018,39(6):2604-2612.
[10]Shimoda M,Hori A,Wands JR,et al.Endocrine sensitivity of estrogen receptor-positive breast cancer is negatively correlated with aspartate-β-hydroxylase expression[J].Cancer Sci,2017,108(12):2454-2461.
[11]Horibata S,Rice EJ,Mukai C,et al.ER-positive breast cancer cells are poised for RET-mediated endocrine resistance[J].PloS One,2018,13(4):e0194023.
[12]Xiao T,Li W,Wang X,et al.Estrogen-regulated feedback loop limits the efficacy of estrogen receptor-targeted breast cancer therapy[J].Proc Natl Acad Sci U S A,2018,115(31):7869-7878.
[13]Liang YK,Zeng D,Xiao YS,et al.MCAM/CD146 promotes tamoxifen resistance in breast cancer cells through induction of epithelialmesenchymal transition,decreased ERαexpression and AKT activation[J].Cancer Lett,2017,386:65-76.
[14]Takeshita T,Yamamoto Y,Yamamoto-Ibusuki M,et al.Prevalence of ESR1 E380Q mutation in tumor tissue and plasma from Japanese breast cancer patients[J].BMC Cancer,2017,17(1):786.
[15]Zhao Y,Laws MJ,Guillen VS,et al.Structurally novel antiestrogens elicit differential responses from constitutively active mutant estrogen receptors in breast cancer cells and tumors[J].Cancer Res,2017,77(20):5602-5613.
[16]Li Z,Levine KM,Bahreini A,et al.Upregulation of IRS1 enhances IGF1 response in Y537S and D538G ESR1 mutant breast cancer cells[J].Endocrinology,2018,159(1):285-296.
[17]Martin LA,Ribas R,Simigdala N,et al.Discovery of naturally occurring ESR1 mutations in breast cancer cell lines modelling endocrine resistance[J].Nat Commun,2017,8(1):1865.
[18]Cairns J,Ingle JN,Wickerham LD,et al.SNPs near the cysteine proteinase cathepsin O gene(CTSO)determine tamoxifen sensitivity in ERα-positive breast cancer through regulation of BRCA1[J].PLoSGenet,2017,13(10):e1007031.
[19]De Cola A,Volpe S,Budani MC,et al.miR-205-5p-mediated downregulation of ErbB/HER receptors in breast cancer stem cells results in targeted therapy resistance[J].Cell Death Dis,2015,6:e1823.
[20]Li J,Lu M,Jin J,et al.miR-449a suppresses tamoxifen resistance in human breast cancer cells by targeting ADAM22[J].Cell Physiol Biochem,2018,50(1):136-149.
[21]Muluhngwi P,Krishna A,Vittitow SL,et al.Tamoxifen differentially regulates miR-29b-1 and miR-29a expression depending on endocrine-sensitivity in breast cancer cells[J].Cancer Lett,2017,388:230-238.
[22]Hayes EL,Lewis-Wambi JS.Mechanisms of endocrine resistance in breast cancer:an overview of the proposed roles of noncoding RNA[J].Breast Cancer Res,2015,17:40.
[23]Xue X,Yang YA,Zhang A,et al.LncRNA HOTAIR enhances ER signaling and confers tamoxifen resistance in breast cancer[J].Oncogene,2016,35(21):2746-2755.
[24]Wu C,Luo J.Long non-coding RNA(lncRNA)urothelial carcinomaassociated 1(UCA1)enhances tamoxifen resistance in breast cancer cells via inhibiting mTOR signaling pathway[J].Med Sci Monit,2016,22:3860-3867.
[25]Peng WX,Huang JG,Yang L,et al.Linc-RoR promotes MAPK/ERK signaling and confers estrogen-independent growth of breast cancer[J].Mol Cancer,2017,16(1):161.
[2]Rugo HS,Rumble RB,Macrae E,et al.Endocrine therapy for hormone receptor-positive metastatic breast cancer:American society of clinical oncology guideline[J].J Clin Oncol,2016,34(25):3069-3103.
[3]García-Becerra R,Santos N,Díaz L,et al.Mechanisms of resistance to endocrine therapy in breast cancer:focus on signaling pathways,miRNAs and genetically based resistance[J].Int J Mol Sci,2012,14(1):108-145.
[4]Chang M.Tamoxifen resistance in breast cancer[J].Biomol Ther(Seoul),2012,20(3):256-267.
[5]Ojo D,Wei F,Liu Y,et al.Factors promoting tamoxifen resistance in breast cancer via stimulating breast cancer stem cell expansion[J].Curr Med Chem,2015,22(19):2360-2374.
[6]Yin L,Pan X,Zhang XT,et al.Downregulation of ER-α36 expression sensitizes HER-2 overexpressing breast cancer cells to tamoxifen[J].Am J Cancer Res,2015,5(2):530-544.
[7]Osborne CK,Bardou V,Hopp TA,et al.Role of the estrogen receptor coactivator AIB1(SRC-3)and HER-2/neu in tamoxifen resistance in breast cancer[J].J Natl Cancer Inst,2003,95(5):353-361.
[8]Shibata T,Watari K,Izumi H,et al.Breast cancer resistance to antiestrogens is enhanced by increased ER degradation and ERBB2 expression[J].Cancer Res,2017,77(2):545-556.
[9]Shen Y,Zhong J,Liu J,et al.Protein arginine N-methyltransferase 2reverses tamoxifen resistance in breast cancer cells through suppression of ER-α36[J].Oncol Rep,2018,39(6):2604-2612.
[10]Shimoda M,Hori A,Wands JR,et al.Endocrine sensitivity of estrogen receptor-positive breast cancer is negatively correlated with aspartate-β-hydroxylase expression[J].Cancer Sci,2017,108(12):2454-2461.
[11]Horibata S,Rice EJ,Mukai C,et al.ER-positive breast cancer cells are poised for RET-mediated endocrine resistance[J].PloS One,2018,13(4):e0194023.
[12]Xiao T,Li W,Wang X,et al.Estrogen-regulated feedback loop limits the efficacy of estrogen receptor-targeted breast cancer therapy[J].Proc Natl Acad Sci U S A,2018,115(31):7869-7878.
[13]Liang YK,Zeng D,Xiao YS,et al.MCAM/CD146 promotes tamoxifen resistance in breast cancer cells through induction of epithelialmesenchymal transition,decreased ERαexpression and AKT activation[J].Cancer Lett,2017,386:65-76.
[14]Takeshita T,Yamamoto Y,Yamamoto-Ibusuki M,et al.Prevalence of ESR1 E380Q mutation in tumor tissue and plasma from Japanese breast cancer patients[J].BMC Cancer,2017,17(1):786.
[15]Zhao Y,Laws MJ,Guillen VS,et al.Structurally novel antiestrogens elicit differential responses from constitutively active mutant estrogen receptors in breast cancer cells and tumors[J].Cancer Res,2017,77(20):5602-5613.
[16]Li Z,Levine KM,Bahreini A,et al.Upregulation of IRS1 enhances IGF1 response in Y537S and D538G ESR1 mutant breast cancer cells[J].Endocrinology,2018,159(1):285-296.
[17]Martin LA,Ribas R,Simigdala N,et al.Discovery of naturally occurring ESR1 mutations in breast cancer cell lines modelling endocrine resistance[J].Nat Commun,2017,8(1):1865.
[18]Cairns J,Ingle JN,Wickerham LD,et al.SNPs near the cysteine proteinase cathepsin O gene(CTSO)determine tamoxifen sensitivity in ERα-positive breast cancer through regulation of BRCA1[J].PLoSGenet,2017,13(10):e1007031.
[19]De Cola A,Volpe S,Budani MC,et al.miR-205-5p-mediated downregulation of ErbB/HER receptors in breast cancer stem cells results in targeted therapy resistance[J].Cell Death Dis,2015,6:e1823.
[20]Li J,Lu M,Jin J,et al.miR-449a suppresses tamoxifen resistance in human breast cancer cells by targeting ADAM22[J].Cell Physiol Biochem,2018,50(1):136-149.
[21]Muluhngwi P,Krishna A,Vittitow SL,et al.Tamoxifen differentially regulates miR-29b-1 and miR-29a expression depending on endocrine-sensitivity in breast cancer cells[J].Cancer Lett,2017,388:230-238.
[22]Hayes EL,Lewis-Wambi JS.Mechanisms of endocrine resistance in breast cancer:an overview of the proposed roles of noncoding RNA[J].Breast Cancer Res,2015,17:40.
[23]Xue X,Yang YA,Zhang A,et al.LncRNA HOTAIR enhances ER signaling and confers tamoxifen resistance in breast cancer[J].Oncogene,2016,35(21):2746-2755.
[24]Wu C,Luo J.Long non-coding RNA(lncRNA)urothelial carcinomaassociated 1(UCA1)enhances tamoxifen resistance in breast cancer cells via inhibiting mTOR signaling pathway[J].Med Sci Monit,2016,22:3860-3867.
[25]Peng WX,Huang JG,Yang L,et al.Linc-RoR promotes MAPK/ERK signaling and confers estrogen-independent growth of breast cancer[J].Mol Cancer,2017,16(1):161.