Cyclin-dependent kinase 7 (CDK7) inhibitors as a novel therapeutic strategy for different molecular types of breast cancer

被引:13
作者
Song, Xue [1 ]
Fang, Chen [1 ]
Dai, Yan [1 ]
Sun, Yang [1 ]
Qiu, Chang [1 ]
Lin, Xiaojie [1 ]
Xu, Rui [1 ]
机构
[1] Guangdong Prov Hosp Chinese Med, Dept Breast Canc, Guangzhou 510120, Peoples R China
关键词
ESTROGEN-RECEPTOR-ALPHA; ALPELISIB PLUS FULVESTRANT; CARBOXY-TERMINAL DOMAIN; TRANSCRIPTIONAL ADDICTION; ESR1; MUTATIONS; FINAL ANALYSIS; OPEN-LABEL; II CTD; TFIIH; PHOSPHORYLATION;
D O I
10.1038/s41416-024-02589-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUNDCyclin-dependent kinase (CDK) 7 is aberrantly overexpressed in many types of cancer and is an attractive target for cancer therapy due to its dual role in transcription and cell cycle progression. Moreover, CDK7 can directly modulate the activities of estrogen receptor (ER), which is a major driver in breast cancer. Breast cancer cells have exhibited high sensitivity to CDK7 inhibition in pre-clinical studies.MethodsIn this review, we provide a comprehensive summary of the latest insights into CDK7 biology and recent advancements in CDK7 inhibitor development for breast cancer treatment. We also discuss the current application of CDK7 inhibitors in different molecular types of breast cancer to provide potential strategies for the treatment of breast cancer.ResultsSignificant progress has been made in the development of selective CDK7 inhibitors, which show efficacy in both triple-negative breast cancer (TNBC) and hormone receptor-positive breast cancer (HR+). Moreover, combined with other agents, CDK7 inhibitors may provide synergistic effects for endocrine therapy and chemotherapy. Thus, high-quality studies for developing potent CDK7 inhibitors and investigating their applications in breast cancer therapy are rapidly emerging.ConclusionCDK7 inhibitors have emerged as a promising therapeutic strategy and have demonstrated significant anti-cancer activity in different subtypes of breast cancer, especially those that have been resistant to current therapies.
引用
收藏
页码:1239 / 1248
页数:10
相关论文
共 119 条
[1]   ARCH domain of XPD, an anchoring platform for CAK that conditions TFIIH DNA repair and transcription activities [J].
Abdulrahman, Wassim ;
Iltis, Izarn ;
Radu, Laura ;
Braun, Cathy ;
Maglott-Roth, Anne ;
Giraudon, Christophe ;
Egly, Jean-Marc ;
Poterszman, Arnaud .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (08) :E633-E642
[2]   Subtyping of Triple-Negative Breast Cancer: Implications for Therapy [J].
Abramson, Vandana G. ;
Lehmann, Brian D. ;
Ballinger, Tarah J. ;
Pietenpol, Jennifer A. .
CANCER, 2015, 121 (01) :8-16
[3]   TFIIH Kinase Places Bivalent Marks on the Carboxy-Terminal Domain of RNA Polymerase II [J].
Akhtar, Md. Sohail ;
Heidemann, Martin ;
Tietjen, Joshua R. ;
Zhang, David W. ;
Chapman, Rob D. ;
Eick, Dirk ;
Ansari, Aseem Z. .
MOLECULAR CELL, 2009, 34 (03) :387-393
[4]   TFIIH is negatively regulated by cdk8-containing mediator complexes [J].
Akoulitchev, S ;
Chuikov, S ;
Reinberg, D .
NATURE, 2000, 407 (6800) :102-106
[5]   The Development of a Selective Cyclin-Dependent Kinase Inhibitor That Shows Antitumor Activity [J].
Ali, Simak ;
Heathcote, Dean A. ;
Kroll, Sebastian H. B. ;
Jogalekar, Ashutosh S. ;
Scheiper, Bodo ;
Patel, Hetal ;
Brackow, Jan ;
Siwicka, Alekasandra ;
Fuchter, Matthew J. ;
Periyasamy, Manikandan ;
Tolhurst, Robert S. ;
Kanneganti, Seshu K. ;
Snyder, James P. ;
Liotta, Dennis C. ;
Aboagye, Eric O. ;
Barrett, Anthony G. M. ;
Coombes, R. Charles .
CANCER RESEARCH, 2009, 69 (15) :6208-6215
[6]   Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2enegative advanced breast cancer: final overall survival results from SOLAR-1 [J].
Andre, F. ;
Ciruelos, E. M. ;
Juric, D. ;
Loibl, S. ;
Campone, M. ;
Mayer, I. A. ;
Rubovszky, G. ;
Yamashita, T. ;
Kaufman, B. ;
Lu, Y-S ;
Inoue, K. ;
Papai, Z. ;
Takahashi, M. ;
Ghaznawi, F. ;
Mills, D. ;
Kaper, M. ;
Miller, M. ;
Conte, P. F. ;
Iwata, H. ;
Rugo, H. S. .
ANNALS OF ONCOLOGY, 2021, 32 (02) :208-217
[7]  
von Minckwitz Gunter, 2017, N Engl J Med, V377, P122, DOI [10.1056/NEJMx170011, 10.1056/NEJMoa1703643]
[8]   p53 directly transactivates Δ133p53α, regulating cell fate outcome in response to DNA damage [J].
Aoubala, M. ;
Murray-Zmijewski, F. ;
Khoury, M. P. ;
Fernandes, K. ;
Perrier, S. ;
Bernard, H. ;
Prats, A-C ;
Lane, D. P. ;
Bourdon, J-C .
CELL DEATH AND DIFFERENTIATION, 2011, 18 (02) :248-258
[9]   Regulation of CDK/cyclin complexes during the cell cycle [J].
Arellano, M ;
Moreno, S .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 1997, 29 (04) :559-573
[10]   The history and future of targeting cyclin-dependent kinases in cancer therapy [J].
Asghar, Uzma ;
Witkiewicz, Agnieszka K. ;
Turner, Nicholas C. ;
Knudsen, Erik S. .
NATURE REVIEWS DRUG DISCOVERY, 2015, 14 (02) :130-146