Identification of clinically significant subtypes of head and neck cancer cells (2007–2009)
Abstract:
Squamous cell carcinoma of the head and neck region (HNSCC) is amongst the top 10 most prevalent cancers. It is a life threatening cancer that is associated with a mortality rate of approximately 40%. Whilst most patients are treated with a combination of surgery, radiation and chemotherapy a significant fraction of patients relapse and eventually succumb to the cancer. The molecular basis for relapse in these patients is still unknown. One possible explanation for treatment failure is the notion that the cancer contains biologically distinct subtypes of cancer cells. Some these cells may respond to therapy whilst a small fraction of cells may not. If this small fraction of resistant cells were able to divide and repopulate the tissue then this would provide an explanation for relapse in these patients. However, as yet no such data has been available to support this argument. Most recently, studies with another cancer called acute myelocytic leukaemia has shown that they do contain a small subtype of cancer cells that are resistant to therapy and can regenerate the disease in patients. These cells have been called tumour initiating cells (TIC). In this application we will use patient tumour samples to try to isolate TICs from HNSCC. We will first determine whether these TICs exist and whether they express markers of normal human stem cells. We will also test whether these TICs are more resistant to chemotherapeutics or radiation than the rest of the tumour cells. In addition we will enrich for these TICs and identify new protein markers that could be used to test patient samples before or after treatment. This would be of considerable assistance in making decisions about treatment choice or prognosis. Since TICs have not been reported in HNSCC previously their identification would lead to a considerable advance in our undesratnding of how these tumours form.
