Molecular landscape and subtype-specific therapeutic response of nasopharyngeal carcinoma revealed by integrative pharmacogenomics

Ren-Bo Ding, Ping Chen, Barani Kumar Rajendran, Xueying Lyu, Haitao Wang, Jiaolin Bao, Jianming Zeng, Wenhui Hao, Heng Sun, Ada Hang-Heng Wong, Monica Vishnu Valecha, Eun Ju Yang, Sek Man Su, Tak Kan Choi, Shuiming Liu, Kin Iong Chan, Ling-Lin Yang, Jingbo Wu, Kai Miao, Qiang Chen, Joong Sup Shim, Xiaoling Xu and Chu-Xia Deng ()
Additional contact information
Ren-Bo Ding: University of Macau
Ping Chen: University of Macau
Barani Kumar Rajendran: University of Macau
Xueying Lyu: University of Macau
Haitao Wang: University of Macau
Jiaolin Bao: University of Macau
Jianming Zeng: University of Macau
Wenhui Hao: University of Macau
Heng Sun: University of Macau
Ada Hang-Heng Wong: University of Macau
Monica Vishnu Valecha: University of Macau
Eun Ju Yang: University of Macau
Sek Man Su: University of Macau
Tak Kan Choi: University of Macau
Shuiming Liu: Kiang Wu Hospital
Kin Iong Chan: Kiang Wu Hospital
Ling-Lin Yang: The Affiliated Hospital of Southwest Medical University
Jingbo Wu: The Affiliated Hospital of Southwest Medical University
Kai Miao: University of Macau
Qiang Chen: University of Macau
Joong Sup Shim: University of Macau
Xiaoling Xu: University of Macau
Chu-Xia Deng: University of Macau

Nature Communications, 2021, vol. 12, issue 1, 1-19

Abstract: Abstract Nasopharyngeal carcinoma (NPC) is a malignant head and neck cancer type with high morbidity in Southeast Asia, however the pathogenic mechanism of this disease is poorly understood. Using integrative pharmacogenomics, we find that NPC subtypes maintain distinct molecular features, drug responsiveness, and graded radiation sensitivity. The epithelial carcinoma (EC) subtype is characterized by activations of microtubule polymerization and defective mitotic spindle checkpoint related genes, whereas sarcomatoid carcinoma (SC) and mixed sarcomatoid-epithelial carcinoma (MSEC) subtypes exhibit enriched epithelial-mesenchymal transition (EMT) and invasion promoting genes, which are well correlated with their morphological features. Furthermore, patient-derived organoid (PDO)-based drug test identifies potential subtype-specific treatment regimens, in that SC and MSEC subtypes are sensitive to microtubule inhibitors, whereas EC subtype is more responsive to EGFR inhibitors, which is synergistically enhanced by combining with radiotherapy. Through combinational chemoradiotherapy (CRT) screening, effective CRT regimens are also suggested for patients showing less sensitivity to radiation. Altogether, our study provides an example of applying integrative pharmacogenomics to establish a personalized precision oncology for NPC subtype-guided therapies.

Date: 2021
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DOI: 10.1038/s41467-021-23379-3

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