Progress and Pitfalls in the Identification of Cancer Stem Cell-Targeting Therapies in Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a highly prevalent and deadly cancer that has not shown improvements in survival rates for many years. Current treatments of HNSCC include surgical resection, radiotherapy, and chemotherapy, which are relatively ineffective for the management of recurrent or metastatic tumors. Cancer stem cells (CSC) within HNSCC offer an attractive therapeutic target for improving the survival rates for such cases, as eliminating the cells responsible for tumor initiation will theoretically prevent the onset of metastasis and recurrence. Since CSCs were initially isolated from HNSCC, there have been a handful of papers published that examine the potential of certain agents to selectively inhibit HNSCC CSCs, although a review of these papers has not yet been performed. Here we review the current literature for potential compounds or particles which have been proposed to selectively target the HNSCC CSC subpopulation. The various agents that have been tested so far include RNA interference, cell-based immunotherapy, antibodies, chemicals, microRNA precursors, and lentiviral microRNA vectors. Although many of these compounds showed considerable promise, few, if any, of the studies provided comprehensive evidence showing that the proposed agents were specific to CSCs and were considerably more effective than conventional therapy (radiation, cisplatin, etc). The proposed treatments in these studies require further investigation in these two regards, especially through rigorous in vivo experimentation, before they can be considered as true potential CSC inhibitors, let alone be considered for use in clinical trials.