Important research into oral and oropharyngeal cancer is underway in many university hospitals, medical centers, and other institutions around the country. Each year, scientists find out more about what causes the disease, how to prevent it, and how to improve treatment.
DNA changes: A great deal of research is being done to learn what DNA changes are responsible for causing cells of the oral cavity and oropharynx to become cancerous. One of the changes often found in DNA of oral cancer cells is a mutation of the p53 gene. The protein produced by this gene normally works to prevent cells from growing too much and helps to destroy cells with DNA damage too extensive for the cells to repair. Damage to p53 DNA can lead to increased growth of abnormal cells and formation of cancers. Recent studies suggest that tests to detect these p53 gene alterations may allow very early detection of oral and oropharyngeal tumors. These tests may also be used to better define surgical margins (check to see if all cancer cells have been removed) and to determine which tumors are most likely to respond to surgery or radiation therapy.
Another DNA change found in some oral cancers is that DNA from a papillomavirus (HPV) becomes mixed together with the patient’s own DNA. Some parts of the HPV DNA instruct the cells to produce proteins that inactivate the p53 protein. Studies are underway to determine whether tests to detect HPV DNA may help in diagnosing these cancers.
Tumor growth factors: Researchers have discovered naturally occurring substances in the body that promote cell growth. These hormone-like substances are called growth factors. Growth factors activate cells by attaching to growth factor receptors, which are present on the outer surface of the cells. Some cancer cells grow especially fast because they contain more growth factor receptors than normal cells do. One of the growth factors that has been linked to oral and oropharyngeal cancers is called epidermal growth factor or EGF. Oral and oropharyngeal cancers with too many EGF receptors tend to be especially aggressive. New drugs that specifically recognize and cells with too many EGF receptors are now being tested in clinical trials. These drugs work by preventing EGF from promoting reproduction of cancer cells, and may also help the patient’s immune system recognize and attack the cancer. Preliminary studies indicate that at least one such drug, called C225, makes radiation therapy more effective in killing head and neck squamous cell cancers.
New chemotherapy: Researchers continue to develop new chemotherapy drugs that might be more effective against advanced oral and oropharyngeal cancer. Intraarterial chemotherapy (injection of drugs into arteries feeding the cancer) is being tested in combination with radiation therapy in an attempt to improve their effectiveness. Another new approach to treating head and neck cancers is intralesional chemotherapy (injecting the drug directly into the tumor). Until recently, success with this approach was limited because the drug tended to spread to nearby tissues and the rest of the body quite quickly. Recent advances in preparing the drug solution, so that it remains localized in the tumor, have renewed the interest in intralesional chemotherapy, and preliminary results have been promising.
New radiotherapy methods: Several clinical trials have been conducted to test the effectiveness of new radiation regimens delivering twice-a-day irradiation in the treatment of oropharyngeal cancer. Higher cure rates have been obtained with a couple of these new regimens. Clinical trials are ongoing to confirm these initial findings. There has also been progress in reducing xerostomia (dry mouth), one of the most important side effects of head and neck radiation therapy. Recent research suggests that amifostine can help reduce this side effect by limiting radiation damage to salivary glands. The drug is given into a vein a few minutes before each radiation treatment. Side effects of amifostine include low blood pressure, nausea, and vomiting. Also, a new protocol for radiating an area from multiple angles, and controlled by new software and blocking shutters, seems to be useful in avoiding the radiation induced destruction of the salivary glands by targeting multiple beams around them, removing the gland from the radiation field.
Vaccines: Most people think of vaccines as a way to prevent infectious diseases such as polio or measles. However, vaccines are being studied as a way to treat people with cancer by helping their immune to recognize and attack the cancer cells. Since some oral and oropharyngeal cancers contain DNA from human papillomaviruses, vaccines against these viruses are being studied as a treatment for these cancers.
Gene therapy: New discoveries about how changes in the DNA of cells in the oral cavity and oropharynx cause these cells to become cancerous are being applied to experimental treatments intended to reverse these changes. For example, clinical trials are testing whether it is possible to replace abnormal tumor suppressor genes (such as the p53 gene) of oral cancer cells with a normal copy, to restore normal growth control. Gene therapies to interfere with growth-stimulating effect of certain papillomaviruses are being developed. Another type of gene therapy adds new genes to the cancer cells to make them more susceptible to being killed by certain drugs.
