Cell cycle regulation and cell growth are interesting targets in the search for new
antitumor agents as these processes are highly disturbed in malignant cells.
E7070 is a novel synthetic sulfon-
amide that targets the G1 phase of the cell cycle and is currently in clinical development for the treatment of solid
tumors. The potential antitumor activity of the compound was discovered through optimization of the structure-activity relationships of a series of
sulfonamide structures.
E7070 causes a blockade in the G1/S transition through inhibition of the activation of both
cyclin-dependent kinase 2 and
cyclin E. Preclinical studies with
E7070 showed activity in multiple
tumor types, most prominently in colon and
lung cancer. A phase I clinical program was conducted with
E7070 evaluating different treatment regimens. Dose-limiting toxicities were hematological, including
neutropenia and
thrombocytopenia. Preliminary results of phase II studies demonstrated limited antitumor activity following treatment with
E7070 as single agent in heavily pretreated patients with non-small cell lung and
colon cancer. Studies evaluating the activity of
E7070 in combination with other chemotherapeutic agents are being conducted.