Parallel genome-wide RNA interference screens to discover new molecular targets for NPC 

- by Prof. Dr. Chee-Onn Leong

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Abstract:

Despite recent advancements in the treatment of nasopharyngeal carcinoma (NPC), targeted therapy remains difficult, particularly for patients with recurrent or metastatic disease. To find new targets for NPC treatment, we conducted parallel genome-wide functional screens and discovered essential genes crucial for NPC cell proliferation and cisplatin resistance. Our findings identified lymphocyte-specific protein tyrosine kinase (LCK) as a major vulnerability for both proliferation and cisplatin resistance. Depleting LCK or treating cells with LCK inhibitors caused tumor-specific cell death and improved cisplatin sensitivity in EBV-positive C666-1 and EBV-negative SUNE1 cells. Our analysis showed that LCK regulates proliferation and cisplatin resistance through the activation of signal transducer and activator of transcription 5 (STAT5). Our research provides a molecular basis for targeting LCK and STAT5 signaling as potential drug targets for NPC management.