Exploiting the head and neck cancer oncogenome: widespread PI3K-mTOR pathway alterations and novel molecular targets

Abstract

Two studies published in this issue of Cancer Discovery describe the emerging mutational landscape of head and neck squamous cell carcinomas (HNSCC) and their genomic and epigenetic alterations, thus identifying novel actionable cancer drivers and predictive biomarkers for targeted therapies. Most genomic alterations in HNSCC converge in a handful of molecular pathways, resulting in cell-cycle deregulation, genomic instability, cell differentiation defects, and persistent mitogenic signaling, the latter involving aberrant phosphoinositide 3-kinase (PI3K)/mTOR pathway activation, thereby rendering HNSCC responsive to PI3K/mTOR inhibitors. Cancer Discov; 3(7); 722-5. ©2013 AACR.

Figure 1. The head and neck cancer oncogenome

Despite the remarkable complexity of genomic alterations found in HNSCC, most of them fall within few major driver-signaling pathways. Alterations found in each key gene are shown. Copy loss refers to homozygous and heterozygous gene deletion. Data were extracted from the publicly available TCGA (The Cancer Genome Atlas) consortium (http://cancergenome.nih.gov/), HNSCC provisional dataset containing CNA, mutational and gene expression data from 295 HNSCC samples.