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

被引：69

作者：

Ding, Ren-Bo ^{[1
,2
]}

Chen, Ping ^{[1
,2
,3
]}

Rajendran, Barani Kumar ^{[1
,2
]}

Lyu, Xueying ^{[1
,2
]}

Wang, Haitao ^{[1
,2
]}

Bao, Jiaolin ^{[1
,2
]}

Zeng, Jianming ^{[1
,2
]}

Hao, Wenhui ^{[1
,2
]}

Sun, Heng ^{[1
,2
]}

Wong, Ada Hang-Heng ^{[1
,2
]}

Valecha, Monica Vishnu ^{[1
,2
]}

Yang, Eun Ju ^{[1
,2
]}

Su, Sek Man ^{[1
,2
]}

Choi, Tak Kan ^{[1
,2
]}

Liu, Shuiming ^{[4
]}

Chan, Kin Iong ^{[4
]}

Yang, Ling-Lin ^{[3
]}

Wu, Jingbo ^{[3
]}

Miao, Kai ^{[1
,2
,5
]}

Chen, Qiang ^{[1
,2
,5
]}

Shim, Joong Sup ^{[1
,2
,5
]}

Xu, Xiaoling ^{[1
,2
,5
]}

Deng, Chu-Xia ^{[1
,2
,5
]}

机构：

[1] Univ Macau, Fac Hlth Sci, Canc Ctr, Zhuhai, Macau Sar, Peoples R China

[2] Univ Macau, Fac Hlth Sci, Ctr Precis Med Res & Training, Zhuhai, Macau Sar, Peoples R China

[3] Southwest Med Univ, Dept Oncol, Affiliated Hosp, Luzhou, Sichuan, Peoples R China

[4] Kiang Wu Hosp, Macau, Macau Sar, Peoples R China

[5] Univ Macau, MOE Frontier Sci Ctr Precis Oncol, Zhuhai, Macau Sar, Peoples R China

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

关键词：

RECEPTOR TYROSINE KINASE; RETROSPECTIVE ANALYSIS; ORGANOID MODELS; COPY NUMBER; RADIOTHERAPY; RON; CHEMORADIOTHERAPY; PHOSPHORYLATION; MICROTUBULES; RESISTANCE;

D O I：

10.1038/s41467-021-23379-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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. Nasopharyngeal carcinoma (NPC) is a malignant cancer type with high morbidity in Asia, and its current molecular classification is insufficient to predict therapy outcomes. Here the authors explore NPC subtype-specific response to therapy with a pharmacogenomics strategy integrating genomics and drug response of patient-derived organoids.

引用

页数：19

共 90 条

[1] Mutational signatures associated with tobacco smoking in human cancer [J].