An experimental compound, ABT-737, that blocks the action of a class of proteins known as the Bcl-2 family, may prove to be a valuable tool in the fight against cancer.

The Bcl-2 family proteins regulate apoptosis (programmed cell death), the natural process by which damaged or unwanted cells die and are cleared from the body. When this process is defective, such as when the Bcl-2 family proteins are present in excess, damaged cells can continue to divide, leading to the formation and growth of tumours. By restoring programmed cell death, ABT-737 not only enhances the effects of chemotherapy and radiation, but also by itself kills particular tumours such as lymphoma and small cell lung carcinoma, according to a new preclinical data published in the current advanced online version of the journal Nature.

"With ABT-737, we have seen encouraging preclinical activity. By restoring apoptosis, the compound caused regression of tumours in animal models," Saul Rosenberg, senior director, Cancer Research, Abbott said adding, "We are particularly encouraged by early results in models of lymphoma and small cell lung cancer, which are very difficult to treat and for which there is a significant unmet medical need for patients."

The data show that ABT-737 binds to the Bcl-2 proteins, and, in effect, restores cell death to cancerous cells. ABT-737 was found to effectively kill certain cancer cell lines, including lymphoma and small cell lung carcinoma. Additionally, Abbott Bcl-2 family inhibitors were found to enhance the effects of chemotherapy and radiation in other types of cancer, such as non-small cell lung cancer.

The Bcl-2 family of proteins plays a central role in regulating apoptosis and, consequently, in tumour formation, tumour growth and resistance to treatment. These proteins are often over expressed in solid tumour. Researchers have been interested in the Bcl-2 proteins since their role in preventing apoptosis was proven more than a decade ago. Pioneering work in structural biology at Abbott established how the Bcl-2 family of proteins interacts with one another. This protein-protein interaction involves a large surface area and has presented significant difficulty in identifying a small-molecule candidate that would potently inhibit the function of these proteins.

These discoveries are the result of a scientific collaboration between Abbott and Idun Pharmaceuticals focused on developing small-molecule treatments for cancer specifically targeting the apoptotic pathway.