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Theranostics 2021; 11(3):1115-1128. doi:10.7150/thno.49716 This issue Cite

Review

Putting the BRK on breast cancer: From molecular target to therapeutics

Hui Li Ang¹, Yi Yuan¹, Xianning Lai², Tuan Zea Tan², Lingzhi Wang¹, Benjamin BoJun Huang¹, Vijay Pandey^3,4, Ruby Yun-Ju Huang⁵, Peter E. Lobie^3,4, Boon Cher Goh^1,6,7, Gautam Sethi⁸, Celestial T. Yap⁹, Ching Wan Chan¹⁰, Soo Chin Lee^2,6,7, Alan Prem Kumar^1,7✉

1. Cancer Science Institute of Singapore and Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
2. Cancer Science Institute of Singapore, National University of Singapore, Singapore.
3. Tsinghua Berkeley Shenzhen Institute and Division of Life Science and Health, Tsinghua University Graduate School, Shenzhen, China.
4. Shenzhen Bay Laboratory, Shenzhen, Guangdong Province, China.
5. School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
6. Department of Haematology-Oncology, National University Health System, Singapore.
7. National University Cancer Institute, National University Health System, Singapore.
8. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
9. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
10. Department of Surgery, University Surgical Cluster, National University Hospital, Singapore.

✉ Corresponding author: Alan Prem Kumar, Cancer Science Institute of Singapore, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 14 Medical Drive, Singapore 117599. Phone: (65) 6516-5456; Fax (65) 6873-9664; E-mail: csiapkedu.sg; phcapkedu.sg. More

Abstract

BReast tumor Kinase (BRK, also known as PTK6) is a non-receptor tyrosine kinase that is highly expressed in breast carcinomas while having low expression in the normal mammary gland, which hints at the oncogenic nature of this kinase in breast cancer. In the past twenty-six years since the discovery of BRK, an increasing number of studies have strived to understand the cellular roles of BRK in breast cancer. Since then, BRK has been found both in vitro and in vivo to activate a multitude of oncoproteins to promote cell proliferation, metastasis, and cancer development. The compelling evidence concerning the oncogenic roles of BRK has also led, since then, to the rapid and exponential development of inhibitors against BRK. This review highlights recent advances in BRK biology in contributing to the “hallmarks of cancer”, as well as BRK's therapeutic significance. Importantly, this review consolidates all known inhibitors of BRK activity and highlights the connection between drug action and BRK-mediated effects. Despite the volume of inhibitors designed against BRK, none have progressed into clinical phase. Understanding the successes and challenges of these inhibitor developments are crucial for the future improvements of new inhibitors that can be clinically relevant.

Keywords: Breast tumor kinase (BRK), hallmarks of cancer, chemical inhibitors, molecular inhibitors, meta-analysis

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