OSI-906 is the first small molecule that selectively targets the IGF-1R receptor to enter Phase I trials − two multi-center dose escalation studies of patients with advanced solid tumors.
The researchers offer their first presentation of the agents structure and preclinical pharmacology at the 2007 AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics meeting.
The insulin-like growth factor receptor (IGF-1R) is an enzyme expressed on the surface of many human cancer cells, and is known to be a driver of tumor growth. OSI-906 blocks IGF-1R activation of the key cancer cell signaling pathways AKT and MAP kinase, researchers say. In laboratory studies of 28 human tumor cell lines, OSI-906 reduced growth of 15 cell lines representative of colorectal, lung, breast, pancreatic, and pediatric tumors and in mouse models. OSI-906 was particularly effective against tumors that are highly IGF-dependent such as colorectal cancers. According to the researchers, OSI-906 not only slowed tumor growth in mice, but decreased the size of some pre-existing tumors.
Blocking IGF-1R may not always be enough because cancer cells can use other receptors to grow, especially the epidermal growth factor receptor (EGFR) which is known to be activated in many human cancers, said Jonathan Pachter, Ph.D., senior director of Cancer Biology at OSI Pharmaceuticals, Inc. Therefore, we hypothesized that the combination of OSI-906 to block IGF-1R together with the anticancer drug Tarceva, which blocks EGFR, would lead to even more effective reduction of cancer growth in cellular and animal models.
In mice with human colorectal cancer tumors, oral administration of OSI-906 or erlotinib alone significantly reduced further growth of the tumors. But when the two drugs were combined, tumor growth was f
|Contact: Greg Lester|
American Association for Cancer Research