MATRIX METALLOPROTEINASES IN LUNG CANCER

$0P50FY2002CANIH

Vanderbilt University, Nashville TN

Investigators

Linked publications & trials

Paper 37400676 Paper 36344823 Paper 30152518 Paper 30017829 Paper 28731711 Paper 27932399 Paper 27852805 Paper 27821489 Paper 27554763 Paper 27253488 Paper 26657862 Paper 26597610 Paper 26431276 Paper 26404003 Paper 26383097 Paper 26325610 Paper 26119936 Paper 26096822 Paper 26083494 Paper 26015408 Paper 25971659 Paper 25870145 Paper 25852169 Paper 25821004 Paper 25733852 Paper 25602689 Paper 25247519 Paper 25173427 Paper 25170644 Paper 25125655 Paper 25054916 Paper 25053577 Paper 25035215 Paper 25028925 Paper 25024357 Paper 24954171 Paper 24893891 Paper 24872542 Paper 24819876 Paper 24713656 Paper 24610826 Paper 24607842 Paper 24599935 Paper 24567661 Paper 24564989 Paper 24564859 Paper 24518087 Paper 24384683 Paper 24302581 Paper 24019492 Paper 24018975 Paper 23913626 Paper 23908357 Paper 23733853 Paper 23704210 Paper 23585862 Paper 23515407 Paper 23338480 Paper 23281772 Paper 23281681 Paper 23224523 Paper 23213057 Paper 23019146 Paper 22933707 Paper 22904681 Paper 22829656 Paper 22798219 Paper 22773810 Paper 22761400 Paper 22561027 Paper 22374995 Paper 22323827 Paper 22232600 Paper 22201803 Paper 22197230 Paper 22173702 Paper 22140546 Paper 22056752 Paper 22028617 Paper 21965228 Paper 21948233 Paper 21866438 Paper 21825014 Paper 21800286 Paper 21760552 Paper 21734175 Paper 21636546 Paper 21613408 Paper 21592456 Paper 21502811 Paper 21487035 Paper 21357624 Paper 21227397 Paper 21215329 Paper 21208983 Paper 21196161 Paper 21172518 Paper 21136798 Paper 20966921 Paper 20855837

Abstract

DESCRIPTION (provided by applicant): Matrix metalloproteinases (MMPs) have been implicated in tumor growth, angiogenesis, invasion, and metastasis. There is extensive preclinical data that inhibition of MMP activity results in a reduction in tumor burden and prolongs the survival of treated animals. Synthetic MMP inhibitors (MMPIs) are currently in Phase III clinical trials in a variety of tumor types, and non-small cell lung cancer (NSCLC) trials in particular have been initiated with several different compounds. The results of the initial studies with the broad spectrum inhibitor marimastat (British Biotech) showed little benefit in advanced pancreatic and gastric cancer, but encouraging results in patients without overt metastases. Studies with the MMPI tanomastat (Bayer Corp.), however, were stopped when preliminary results from an adjuvant small cell lung cancer (SCLC) trial demonstrated that the MMPI was performing worse than placebo. These results raised the realization that very little is known about the role of MMPs in lung cancer development and progression. This proposal is designed to test the hypothesis that MMPs are valid therapeutic targets for lung cancer, and to determine the MMP family members that represent the most appropriate targets for MMPIs in NSC and SC lung cancer. The following specific aims are proposed: 1) Determine the expression profile of MMP transcripts and protein in SCLC and NSCLC samples and associate the expression profile with response to MMPI treatment. 2) Determine if MMPIs inhibit MMP activity in lung cancer patients using an ex vivo MMP activity assay, and 3) Determine the efficacy of MMPIs in chemically-induced and orthotopic preclinical models of lung cancer. The availability of mice that are null for several MMP family members provides the opportunity to examine the role of specific MMP family members in these model systems. These studies represent translational research that will guide the selection and application of selective MMPIs to the treatment of lung cancer.

View original record on NIH RePORTER →