Gene expression profiles indicative of response to cisplatin.

摘要

For cancer patients, earlier identification and initiation of the optimal treatment for their disease would result in increased survival time and decreased chances that they would be subjected to the systemic toxicities of chemotherapy without experiencing a significant decrease in their cancer. One way that a physician might be able to determine if a patient's tumor is likely to display a clinical response to a specific treatment is to examine the gene expression profile of the tumor a short time after initiation of the treatment. If there existed a gene expression profile that was known to be correlated with response to the treatment, the physician could compare that profile to the profile obtained from the patient's tumor to ascertain the likelihood of achieving a response. As a first step towards assessing the feasibility of this approach to cancer therapy, experiments were performed to determine if it is possible to identify a signature gene expression profile which is correlated with response to cisplatin in vitro. Head and neck squamous cell carcinoma (HNSCC) cells were treated with a dose of cisplatin sufficient to induce growth arrest and/or death in the majority of the cells in the treated population of cells. Expression profiling of three HNSCC cell lines treated as such indicated that although the expression profiles for each cell line were quite different overall, a common expression profile could be identified. In an additional study, gene expression profiles were obtained from treated populations of tumor cells that simulated responding samples, as well as from treated populations that simulated non-responding samples. These profiles were used to demonstrate how expression profiles could discriminate between populations of cells that were responding to cisplatin and those that were not. The results obtained from the studies described in this dissertation suggest that gene expression profiling might be a clinically useful tool that could assist physicians in determining if a patient's tumor will respond to cisplatin. In addition, the gene expression profiling experiments that were performed resulted in the discovery of several genes as being potentially new participants in the cellular injury response to cisplatin.