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中华乳腺病杂志(电子版) ›› 2021, Vol. 15 ›› Issue (04) : 247 -251. doi: 10.3877/cma.j.issn.1674-0807.2021.04.011

所属专题: 文献

综述

细胞周期蛋白依赖性激酶4/6抑制剂在乳腺癌治疗中的应用
徐颖1, 孙强1,()   
  1. 1. 100005 中国医学科学院北京协和医学院北京协和医院乳腺外科
  • 收稿日期:2020-11-23 出版日期:2021-09-08
  • 通信作者: 孙强

Inhibitors of cyclin-dependent kinase 4/6 for breast cancer treatment

Ying Xu1, Qiang Sun1()   

  • Received:2020-11-23 Published:2021-09-08
  • Corresponding author: Qiang Sun
引用本文:

徐颖, 孙强. 细胞周期蛋白依赖性激酶4/6抑制剂在乳腺癌治疗中的应用[J]. 中华乳腺病杂志(电子版), 2021, 15(04): 247-251.

Ying Xu, Qiang Sun. Inhibitors of cyclin-dependent kinase 4/6 for breast cancer treatment[J]. Chinese Journal of Breast Disease(Electronic Edition), 2021, 15(04): 247-251.

乳腺癌是女性常见的恶性肿瘤,激素受体/HER-2阴性乳腺癌是乳腺癌的常见类型。细胞周期蛋白依赖性激酶(CDK)4/6抑制剂为该类型乳腺癌的治疗带来了新的希望。笔者对CDK4/6抑制剂在乳腺癌治疗中的研究进展、相关临床试验、应用现状及耐药性等问题等进行综述,供同行参考。

图1 细胞周期蛋白依赖性激酶4/6抑制剂抑制细胞增殖的分子机制
[1]
Torre LA, Islami F, Siegel RL, et al.Global cancer in women: burden and trends[J]. Cancer Epidemiol Biomarkers Prev, 2017, 26(4): 444-457.
[2]
Migliaccio I, Malorni L, Hart CD, et al.Endocrine therapy considerations in postmenopausal patients with hormone receptor positive, human epidermal growth factor receptor type 2 negative advanced breast cancers[J]. BMC Med, 2015, 13: 46.
[3]
Joy AA, Ghosh M, Fernandes R, et al.Systemic treatment approaches in her2-negative advanced breast cancer-guidance on the guidelines[J]. Curr Oncol, 2015, 22(Suppl 1): S29-S42.
[4]
Daly MB, Pal T, Berry MP, et al. Genetic/familial high-risk assessment: breast, ovarian, and pancreatic, version 2.2021, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2021, 19(1):77-102.
[5]
U.S. Food and Drug Administration. Palbocilib(IBRANCE)[EB/OL].[2020-11-10].

URL    
[6]
U.S. Food and Drug Administration. Ribocilib(Kisqali) [EB/OL].[2020-11-10].

URL    
[7]
U.S. Food and Drug Administration.FDA aprroves abemaciclib for HR-positive,HER2-negative breast cancer[EB/OL].[2020-11-10].

URL    
[8]
Cristofanilli M, Turner NC, Bondarenko I, et al.Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial[J]. Lancet Oncol, 2016, 17(4): 425-439.
[9]
Malumbres M.Cyclin-dependent kinases[J]. Genome Biol, 2014, 15(6): 122.
[10]
Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer[J]. N Engl J Med, 2016, 375(18): 1738-1748.
[11]
Otto T, Sicinski P.Cell cycle proteins as promising targets in cancer therapy[J]. Nat Rev Cancer, 2017, 17(2): 93-115.
[12]
Shapiro GI.Cyclin-dependent kinase pathways as targets for cancer treatment[J]. J Clin Oncol, 2006, 24(11): 1770-1783.
[13]
Canavese M, Santo L, Raje N.Cyclin dependent kinases in cancer: potential for therapeutic intervention[J]. Cancer Biol Ther, 2012, 13(7): 451-457.
[14]
Benson C, White J, De Bono J, et al.A phase I trial of the selective oral cyclin-dependent kinase inhibitor seliciclib (CYC202; R-Roscovitine), administered twice daily for 7 days every 21 days[J]. Br J Cancer, 2007, 96(1): 29-37.
[15]
Sausville EA, Arbuck SG, Messmann R, et al. Phase I trial of 72-hour continuous infusion UCN-01 in patients with refractory neoplasms[J]. J Clin Oncol, 2001, 19(8): 2319-2333.
[16]
Kalra S, Joshi G, Munshi A, et al.Structural insights of cyclin dependent kinases: Implications in design of selective inhibitors[J]. Eur J Med Chem, 2017, 142: 424-458.
[17]
Toogood PL, Harvey PJ, Repine JT, et al.Discovery of a potent and selective inhibitor of cyclin-dependent kinase 4/6[J]. J Med Chem, 2005, 48(7): 2388-2406.
[18]
Fry DW, Harvey PJ, Keller PR, et al.Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts[J]. Mol Cancer Ther, 2004, 3(11): 1427-1438.
[19]
Finn RS, Dering J, Conklin D, et al.PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro[J]. Breast Cancer Res, 2009, 11(5): R77.
[20]
Beaver JA, Amiri-Kordestani L, Charlab R, et al. FDA approval: palbociclib for the treatment of postmenopausal patients with estrogen receptor-positive, HER2-negative metastatic breast cancer[J]. Clin Cancer Res, 2015, 21(21): 4760-4766.
[21]
Finn RS, Crown JP, Lang I, et al.The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study[J]. Lancet Oncol, 2015, 16(1): 25-35.
[22]
Finn RS, Martin M, Rugo HS, et al.Palbociclib and letrozole in advanced breast cancer[J]. N Engl J Med, 2016, 375(20): 1925-1936.
[23]
Johnston S, Puhalla S, Wheatley D, et al.Randomized phase II study evaluating palbociclib in addition to letrozole as neoadjuvant therapy in estrogen receptor-positive early breast cancer: PALLET trial[J]. J Clin Oncol, 2019, 37(3): 178-189.
[24]
Mayer EL, Dueck AC, Martin M, et al.Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study[J]. Lancet Oncol, 2021, 22(2): 212-222.
[25]
DeMichele A, Clark AS, Tan KS, et al.CDK 4/6 inhibitor palbociclib (PD0332991) in Rb+ advanced breast cancer: phase II activity, safety, and predictive biomarker assessment[J]. Clin Cancer Res, 2015, 21(5): 995-1001.
[26]
Pandey K, An HJ, Kim SK, et al.Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer: A review[J]. Int J Cancer, 2019, 145(5): 1179-1188.
[27]
Curigliano G, Gomez Pardo P, Meric-Bernstam F, et al.Ribociclib plus letrozole in early breast cancer: A presurgical, window-of-opportunity study[J]. Breast, 2016, 28: 191-198.
[28]
Slamon DJ, Neven P, Chia S, et al.Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3[J]. J Clin Oncol, 2018, 36(24): 2465-2472.
[29]
Tripathy D, Im SA, Colleoni M, et al.Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial[J]. Lancet Oncol, 2018, 19(7): 904-915.
[30]
Gelbert LM, Cai S, Lin X, et al.Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine[J]. Invest New Drugs, 2014, 32(5): 825-837.
[31]
Turtle CJ, Hay KA, Hanafi LA, et al.Durable molecular remissions in chronic lymphocytic leukemia treated with CD19-specific chimeric antigen receptor-modified T cells after failure of ibrutinib[J]. J Clin Oncol, 2017, 35(26): 3010-3020.
[32]
Spring L, Bardia A, Modi S.Targeting the cyclin D-cyclin-dependent kinase (CDK) 4/6-retinoblastoma pathway with selective CDK 4/6 inhibitors in hormone receptor-positive breast cancer: rationale, current status, and future directions[J]. Discov Med, 2016, 21(113): 65-74.
[33]
Dickler MN, Tolaney SM, Rugo HS, et al.MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR(+)/HER2(-) metastatic breast cancer[J]. Clin Cancer Res, 2017, 23(17): 5218-5224.
[34]
Sledge GW Jr, Toi M, Neven P, et al.MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy[J]. J Clin Oncol, 2017, 35(25): 2875-2884.
[35]
Johnston S, Martin M, Di Leo A, et al.MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer[J]. NPJ Breast Cancer, 2019, 5: 5.
[36]
Johnston SRD, Harbeck N, Hegg R, et al.Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+,HER2-,node-positive, high-risk, early breast cancer (monarchE)[J]. J Clin Oncol, 2020, 38(34): 3987-3998.
[37]
Guarducci C, Bonechi M, Boccalini G, et al.Mechanisms of resistance to CDK4/6 inhibitors in breast cancer and potential biomarkers of response[J]. Breast Care (Basel), 2017, 12(5): 304-308.
[38]
Cen L, Carlson BL, Schroeder MA, et al.p16-Cdk4-Rb axis controls sensitivity to a cyclin-dependent kinase inhibitor PD0332991 in glioblastoma xenograft cells[J]. Neuro Oncol, 2012, 14(7): 870-881.
[39]
Condorelli R, Spring L, O’Shaughnessy J, et al.Polyclonal RB1 mutations and acquired resistance to CDK 4/6 inhibitors in patients with metastatic breast cancer[J]. Ann Oncol, 2018, 29(3): 640-645.
[40]
Konecny GE, Winterhoff B, Kolarova T, et al.Expression of p16 and retinoblastoma determines response to CDK4/6 inhibition in ovarian cancer[J]. Clin Cancer Res, 2011, 17(6): 1591-1602.
[41]
Dean JL, McClendon AK, Hickey TE, et al.Therapeutic response to CDK4/6 inhibition in breast cancer defined by ex vivo analyses of human tumors[J]. Cell Cycle, 2012, 11(14): 2756-2761.
[42]
Sahores A, May M, Sequeira GR, et al.Targeting FGFR with BGJ398 in breast cancer: effect on tumor growth and metastasis[J]. Curr Cancer Drug Targets, 2018, 18(10): 979-987.
[43]
Turner N, Pearson A, Sharpe R, et al.FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer[J]. Cancer Res, 2010, 70(5): 2085-2094.
[44]
Takeshita T, Yamamoto Y, Yamamoto-Ibusuki M, et al.Clinical significance of plasma cell-free DNA mutations in PIK3CA, AKT1, and ESR1 gene according to treatment lines in ER-positive breast cancer[J]. Mol Cancer, 2018, 17(1): 67.
[45]
Jansen VM, Bhola NE, Bauer JA, et al.Kinome-wide RNA interference screen reveals a role for PDK1 in acquired resistance to CDK4/6 inhibition in ER-positive breast cancer[J]. Cancer Res, 2017, 77(9): 2488-2499.
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