Molecular landscape and subtype-specific therapeutic response of nasopharyngeal carcinoma revealed by integrative pharmacogenomics.
Ren-Bo DingPing ChenBarani Kumar RajendranXueying LyuHaitao WangJiaolin BaoJianming ZengWenhui HaoHeng SunAda Hang-Heng WongMonica Vishnu ValechaEun Ju YangSek Man SuTak Kan ChoiShuiming LiuKin Iong ChanLing-Lin YangJingbo WuKai MiaoQiang ChenJoong Sup ShimXiaoling XuChu-Xia DengPublished in: Nature communications (2021)
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.
Keyphrases
- epithelial mesenchymal transition
- adverse drug
- small cell lung cancer
- end stage renal disease
- early stage
- locally advanced
- genome wide
- ejection fraction
- cell cycle
- network analysis
- peritoneal dialysis
- clinical decision support
- radiation induced
- dna damage
- gene expression
- single molecule
- palliative care
- signaling pathway
- epidermal growth factor receptor
- rectal cancer
- dna methylation
- cardiac resynchronization therapy
- risk assessment
- drug induced
- squamous cell carcinoma
- oxidative stress
- climate change
- smoking cessation
- cell migration
- combination therapy
- transcription factor
- atrial fibrillation