Angiogenin-mediated ribosomal RNA transcription as a molecular target for treatment of head and neck squamous cell carcinoma.

Squamous cell carcinoma of the head and neck (HNSCC) is the eighth most common disease, affecting approximately 640,000 patients worldwide each year. Despite recent advances in surgery, radiotherapy, and chemotherapy, the overall cure for patients with HNSCC has remained at less than 50% for many decades. Patients with recurrent and metastatic disease have a median survival of only 6-10 months. Systemic chemotherapy is the only treatment option for those patients. New treatment options are thus desperately needed to supplement, complement, or replace currently available therapies. New agents that target molecular and cellular pathways of the disease pathogenesis of HNSCC are promising candidates. One class of these new agents is angiogenesis inhibitors that have been proven effective in the treatment of advanced colorectal, breast, and non-small cell lung cancers. Similar to other solid tumors, angiogenesis plays an important role in the pathogenesis of HNSCC. A number of angiogenic factors including vascular endothelial growth factor (VEGF) and angiogenin (ANG) have been shown to be significantly upregulated in HNSCC. Among them, ANG is unique in which it is a ribonuclease that regulates ribosomal RNA (rRNA) transcription. ANG-stimulated rRNA transcription has been shown to be a general requirement for angiogenesis induced by other angiogenic factors. ANG inhibitors have been demonstrated to inhibit angiogenesis and tumor growth induced not only by ANG but also by other angiogenic factors. As the role of ANG in HNSCC is being unveiled, the therapeutic potential of ANG inhibitors in HNSCC is expected.