NEW YORK (Reuters Health) - ABT-737, an inhibitor of Bcl-2 family proteins, kills cells from various cancer cell lines in vitro and induces regression of established solid tumors in mice, according to a report in the May 15th issue of Nature.
“These results suggest that ABT-737 and related compounds could potentially be used as a single agent or in combination with other agents to treat cancer,” Dr. Stephen W. Fesik from Abbott Laboratories, Abbott Park, Illinois told Reuters Health.
Dr. Fesik and colleagues discovered ABT-737, a small-molecule inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-XL, and Bcl-w, and tested its effects in various carcinoma lines, patient-derived cells, and animal models.
ABT-737 and related compounds displayed synergism with chemotherapy and radiation in a variety of tumor cell lines, the authors report, and showed potent single-agent activity against cell lines representing lymphoid malignancies and small-cell lung cancer.
ABT-737 induced apoptosis in 13 of 15 chronic lymphocytic leukemia B-cell specimens derived from patients, the report indicates.
In animal models of cancer, the researchers note, ABT-737 significantly improved survival from disseminated disease and caused complete regression of established small-cell lung carcinoma tumor xenografts in mice.
ABT-737 was well tolerated in all in vivo experiments, causing only a reduction in platelets and lymphocytes in mice treated for 21 days, the investigators report.
“Although it’s too early to say how the compounds will behave in the clinic, our preclinical data indicate that our Bcl-2 family inhibitors restored apoptosis and led to tumor regression -- durable regression in some cases,” Dr. Fesik said. “We are hopeful that our compounds will add new weapons to fight a wide variety of cancers.”
“We are actively pursuing both intravenous and oral formulations of ABT-737 and related compounds, and they continue to be studied preclinically, with the goal of bringing them to the clinic,” Dr. Fesik added.
Source: Nature 2005.doi:10.1038/nature03579. [ Google search on this article ]
MeSH Headings:Proto-Oncogene Proteins: Proto-Oncogene Proteins c-bcl-2Copyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
