New insights into nasopharyngeal carcinoma

Abstract

Nasopharyngeal carcinoma (NPC) is a cancer of special importance to Southern Chinese, who have the highest incidence of this cancer worldwide. Its peak incidence is amongst individuals only in their 40’s and 50’s in age. We have been interested in understanding the genetic etiology of this cancer and trying to find new approaches for its diagnosis and treatment. Using next-generation sequencing (NGS) approaches, we have studied NPC genetic susceptibility and molecular landscape alterations hallmarking this cancer. We have utilized a cohort of early-age onset NPC cases and NPC cases having a family history of this cancer to identify candidate cancer predisposition genes. The macrophage stimulating receptor 1 (MST1R) gene mapping to chromosome 3p21.3 was found to play an important role in NPC development. Using whole-exome sequencing approaches, we also analyzed genomic changes in primary, recurrent, and metastatic lymph node NPC tumors. These studies identified key NF-kB pathway regulators and other important cell cycle and chromatin modification regulators contributing to NPC development and metastasis. Due to its innocuous symptoms, NPC is usually not diagnosed until late in the progression of this cancer, when treatment prospects are decreased. We are also utilizing non-invasive liquid biopsies to identify the circulating tumor cells (CTCs) from patients with NPC. CTC enumeration provides the capacity for real-time monitoring of treatment efficacy. We are also able to determine the genetic profiles of patients before, during and after clinical treatment. Using this novel approach, we will be able to examine important questions such as tumor heterogeneity and development of drug resistance. We expect our studies to provide new insights into NPC development and spread and to usher in the era of personalized care of these patients.