CHEMORADIATION RESPONSE--LARYNGEAL /HYPOPHARYNGEAL CA

$0P50FY2002CANIH

University Of Michigan At Ann Arbor, Ann Arbor MI

Investigators

Linked publications & trials

Paper 35416374 Paper 35170737 Paper 34689150 Paper 34111559 Paper 33835136 Paper 33320960 Paper 33203919 Paper 33203436 Paper 32406560 Paper 32041834 Paper 31989702 Paper 31835136 Paper 31569808 Paper 31486841 Paper 31315911 Paper 30862188 Paper 30775826 Paper 30548484 Paper 30527240 Paper 30498096 Paper 30291798 Paper 30186960 Paper 29800815 Paper 29769207 Paper 29756240 Paper 29604042 Paper 29362132 Paper 29245982 Paper 29227715 Paper 29145573 Paper 29112231 Paper 29053175 Paper 28949800 Paper 28928286 Paper 28608731 Paper 28266024 Paper 28236344 Paper 28168879 Paper 28152117 Paper 27939002 Paper 27899422 Paper 27872102 Paper 27780858 Paper 27738310 Paper 27613928 Paper 27612423 Paper 27554375 Paper 27553942 Paper 27550999 Paper 27432208 Paper 27422711 Paper 27345657 Paper 27285754 Paper 27225873 Paper 27151511 Paper 27117272 Paper 27091409 Paper 26936915 Paper 26930647 Paper 26892642 Paper 26879675 Paper 26849095 Paper 26783960 Paper 26614223 Paper 26569309 Paper 26566081 Paper 26518708 Paper 26484687 Paper 26476077 Paper 26449187 Paper 26426565 Paper 26287605 Paper 26121939 Paper 26094074 Paper 26077310 Paper 25931286 Paper 25914344 Paper 25681087 Paper 25677579 Paper 25572737 Paper 25468899 Paper 25428916 Paper 25283344 Paper 25280025 Paper 25251643 Paper 25177526 Paper 25126449 Paper 25082736 Paper 25078284 Paper 24962247 Paper 24894502 Paper 24830761 Paper 24816422 Paper 24803391 Paper 24709421 Paper 24709418 Paper 24700717 Paper 24686166 Paper 24565983 Paper 24533454

Abstract

DESCRIPTION (provided by applicant): Prior work on patient samples and tumor cell lines has shown that overexpression and mutation of p53 and low expression of the apoptosis-blocking proteins Bcl-xL and Bcl-2 correlate with chemotherapy response and successful organ preservation using sequential chemoradiation. The next step is to prospectively evaluate these molecular markers in clinical trials for their predictive value for chemotherapy response, organ preservation, and survival in order to select patients properly and avoid unnecessary morbidity and therapeutic redundancy. These data will allow the rationale design of future treatment paradigms where patients are selected for optimum therapy based upon the molecular profile of the tumors. A comprehensive research program is proposed to investigate the role of the p53 tumor suppressor gene and the Bcl-2 family of genes in the chemo/radiosensitivity of advanced laryngeal and hypopharyngeal squamous cell carcinoma. The hypothesis to be tested is that a combination of p53 mutation status and expression of the Bcl-2 family of genes determines the mechanism of cell death and response to chemoradiation regimens. Concurrent with the clinical investigations, in vitro studies will be performed to directly assess the impact of manipulation of p53 and Bcl-2 status upon chemotherapy and radiation sensitivity. We plan to test our hypothesis by executing the following specific aims: (1) To prospectively determine if a combination of apoptosis gene markers (p53, Bcl-2, Bcl-xl) predict response to neoadjuvant chemotherapy, organ preservation and survival in patients with advanced laryngeal and hypopharyngeal cancer; and (2) To test the hypothesis that cisplatin and radiation resistance in tumor cells can be overcome by direct inhibition of apoptosis-blocking genes using gene transfection strategies and small molecule inhibitors of Bcl-2 and Bcl-xL in in vitro model systems. Furthermore, we will test the hypothesis that transfection of dominantnegative p53 mutations will enhance the sensitivity of HNSCC cell lines to radiation and chemoradiation.

View original record on NIH RePORTER →