The overall goal of this program project is to increase the cure rate of human cancer. The approaches to this specific goal will include the development of drugs with new mechanisms of action against tumor growth and development, continued exploration of the problem of drug resistance by looking at new chemosensitizers which circumvent the resistance pathway, utilization of new peptide technology to develop new treatments for lymphoma and other malignant disorders and finally the transfer of laboratory findings into the clinical treatment are for several Phase I trials. Specific aims: 1. Develop new drugs with novel mechanisms of action against cancer. 2. Investigate mechanisms of drug resistance and develop means of circumventing it in hematologic malignancies and selected solid tumors and relate these approaches to clinical trials carried out in this program project grant. 3. Apply the Random Peptide Synthesis and Testing (RPST) technology to the identification of novel peptides as (a) inhibitors of cancer associated enzymes matrilysin and phosphatidyl inositol phospholipase C, and (b) to identify patient-specific peptides which bind to cell surface idiotypic immunoglobulin in B-cell non-Hodgkin's lymphoma and investigate the discovered peptides as potential therapy for lymphoma. 4. Develop new clinical therapeutic programs based on clinical and laboratory observations and by correlating clinical observations. Clinical observations will be correlated with laboratory results and hypotheses generated regarding tumor progression and response to therapy. Additionally, new laboratory initiatives will be based on clinical observations and will be used as part of the hypothesis testing procedure.