Other Studies

Novel Signal Transduction Inhibitors 
We have embarked on a collection of studies assessing novel designer small molecules that inhibit autophosphorylation of members of the erbB family of transmembrane receptors (erbB-1 Œepidermal growth factor receptor; EGFr,erbB-2 ŒHER-2/neu, erbB-3, erbB-4).  In this study - A phase I Clinical and Pharmacokinetic Evaluation of Oral CI1033 Given as a Single Dose Daily in Patients with Advanced Nonhematological Malignancies – attempts will be made to determine a submaximal dose that inhibits erbB family autophosphorylation in the patients’ target tumors and normal skin, to aid in the selection of the recommended phase II dose.  Other novel molecules (e.g., OSI-774, Iressa, C225 etc…) are forthcoming and would be used in conjunction with chemotherapy.
 

Novel Small Molecules Targeting Topoisomerases
The anti-tumor activities of DX-8951f have been studied both in vitro and in vivo in a number of different model systems.  DX-8951f was approximately three times more potent than SN-38 (the active metabolite of CPT-11), ten times more potent than topotecan, and twenty times more potent than camptothecin as an inhibitor of topoisomerase I activity in vitro, and five times more potent than SN-38 as an inhibitor of DNA synthesis.  In cell-based cytotoxicity assays, DX-8951f was three to ten times more active than SN-38, topotecan, or camptothecin in its anti-proliferative activity against a wide range of human breast, colon, gastrointestinal, and lung tumor cell lines, and a number of other mammalian tumor cell lines as well.  DX-8951f was also effective in inhibiting the growth of clonogenic cells from human head and neck, liver, non-small cell lung, breast, colon, ovarian and prostate tumors in vitro. At Montefiore, we are studying a phase I combination of Dx8951f with gemcitabine - A Phase I Study of Combination DX-8951f and Gemcitabine in Patients with Advanced Solid tumors.