Parallel genome-wide RNAi screens identify lymphocyte-specific protein tyrosine kinase (LCK) as a targetable vulnerability of cell proliferation and chemoresistance in nasopharyngeal carcinoma

Kitson Liew, Gibson Qi Sheng Yu, Lesley Jia Wei Pua, Li Zhe Wong, Shiau Ying Tham, Ling-Wei Hii, Wei-Meng Lim, Brian Ming OuYong, Chin King Looi, Chun-Wai Mai, Felicia Fei-Lei Chung, Lu Ping Tan, Munirah Ahmad, Alan Soo-Beng Khoo, Chee-Onn Leong

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Despite recent in advances in the management of nasopharyngeal carcinoma (NPC), development of targeted therapy remains challenging particularly in patients with recurrent or metastatic disease. To search for clinically relevant targets for the treatment of NPC, we carried out parallel genome-wide functional screens to identified essential genes that are required for NPC cells proliferation and cisplatin resistance. We identified lymphocyte-specific protein tyrosine kinase (LCK) as a key vulnerability of both proliferation and cisplatin resistance. Depletion of endogenous LCK or treatment of cells with LCK inhibitor induced tumor-specific cell death and synergized cisplatin sensitivity in EBV-positive C666-1 and EBV-negative SUNE1 cells. Further analyses demonstrated that LCK is regulating the proliferation and cisplatin resistance through activation of signal transducer and activator of transcription 5 (STAT5). Taken together, our study provides a molecular basis for targeting LCK and STAT5 signaling as potential druggable targets for the management of NPC.

Original languageEnglish
Pages (from-to)81-90
Number of pages10
JournalCancer Letters
Publication statusPublished - 28 Apr 2021
Externally publishedYes


  • Drug combination
  • LCK
  • Nasopharyngeal carcinoma
  • NPC
  • STAT5

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