Traditionally, surgery and radiation were the only treatments thought to be effective against oral cancer, with chemotherapy used as a palliative measure. Within the last decade scientists have found that certain drugs do indeed work against oral cancer. Researchers are now using radiation and chemotherapy in tandem, giving cancer a 'one-two' punch in an effort to knock it out. One of the newest drugs in the oral cancer treatment armamentarium is paclitaxel (Taxol, Bristol-Myers Squibb Co.), which has shown some success in treating other cancers. Currently, clinical researchers are studying paclitaxel as a treatment for oral cancer, using the drug by itself and in combination with other chemotherapeutic agents and radiation therapy.
Long before drugs are used in the clinic, they undergo extensive testing for safety and efficacy. Countless compounds initially thought to have some activity against cancer ultimately fail. But a few, like paclitaxel, do not. So researchers continue to screen thousands of compounds searching for those that show evidence of antitumor activity. Recently, NIDCR and the National Cancer Institute have become partners in the effort to identify natural or synthetic agents that demonstrate activity against squamous cell carcinoma. NIDCR is now testing the ability of certain agents-already shown to have antitumor activity by an NCI cell line assay -- to diminish growth of squamous cell carcinoma lines in vitro and in vivo. The scientists hope to confirm the efficacy of these compounds and move them a step closer to clinical testing.
Other research is focused on inventing new systems to test potentially therapeutic compounds. NIDCR-funded investigators at the M.D. Anderson Cancer Center are developing a unique tissue slice organ culture (TSOC) that consists of normal, premalignant, and malignant human oral tissue slices kept alive in the laboratory. The advantage of the TSOC is that it preserves tissue organization, cell interaction, and cell function more so than do cultured cell lines. Because the model essentially mimics in vivo conditions, it is ideal for testing numerous agents in various amounts and combinations. Oral cancer research has been hindered by the methods usually employed to investigate growth and differentiation of normal and premalignant oral cells. Culturing normal oral cells is complicated, and no successful method for culturing genuine premalignant oral cells exists. The scientists hope to establish the TSOC system as the standard for examining normal, premalignant, and malignant oral tissues.
Using the TSOC the scientists are looking at the ability of vitamin A analogues (retinoids) and sodium butyrate, a four-carbon fatty acid, alone or in combination, to reverse aberrations in cell growth and differentiation. Scientists already know that one retinoid, called isotretinoin, can reverse premalignant oral lesions; however, the analogue has side effects that preclude its prolonged use. One of the research goals is to identify other retinoids with similar or better efficacy than isotretinoin, and analyze them to determine whether they may have fewer side effects. If so, these compounds could be candidates for clinical testing. The scientists also hope to investigate whether butyrate might be effective in preventing or treating oral malignancies.
Complementing the vast array of laboratory experiments are clinical studies aimed at testing new cancer treatments or helping to improve the quality of life for patients living with the disease. At the University of Chicago and Northwestern University, another NIDCR-NCI Oral Cancer Research Center, scientists in one clinical study are looking at the chemotherapeutic effects of 5-fluorouracil (5-FU) in combination with radiation therapy. One problem with using this drug has been that the enzyme dihydropyrimidine dehydrogenase (DPD) can degrade 5-FU and lower its level in the body below a therapeutic range. To circumvent this problem, the scientists are testing 5-FU in combination with a chemical that blocks DPD action, which might keep the cancer-fighting drug at its therapeutic level. Scientists will correlate the activity of 5-FU with enzyme activity and with patient response and survival. By conducting studies aimed at elucidating the idiosyncrasies of this powerful drug, the researchers hope to learn how to use it most effectively against oral cancer.
In patients with advanced cancer, one of the primary goals is to reduce
the symptoms of large tumors and preserve organ function, thus maintaining
or improving quality of life. This is the focus of another study at the
University of Chicago-Northwestern University. Clinicians are analyzing
the effects of high-dose radiotherapy combined with chemotherapies on tongue
strength and swallowing function in patients with advanced cancer. Using
the latest imaging techniques, scientists are able to observe even minute
changes in organ function.