Companies Waver in Efforts To Target Transforming Growth Factor β in Cancer

Extract

More than 30 years after its discovery, transforming growth factor β (TGF-β) engages developmental biologists, immunologists, cell biologists, and cancer researchers. New findings are reported weekly for this multifunctional cytokine family. In cancer, researchers continue to deconstruct TGF-β's dual role as a tumor suppressor and promoter. Interest in its biology is greater than ever.

Unfortunately, the same can't be said about therapies targeting TGF-β in cancer. Earlier this decade, spurred by reports that TGF-β inhibition was safe and effective in animal models, many drug and biotech companies launched programs to develop TGF-β inhibitors. But several of these programs have recently been abandoned, and most companies that remain in the race are proceeding slowly and cautiously ( see sidebar). The future of TGF-β therapy, once so bright, is now in doubt.

From the Start

TGF-β and cancer were linked from the start. In 1978, Joe De Larco, Ph.D., and George Todaro, M.D., at the National Cancer Institute partially purified a substance that allowed normal cells to form colonies in soft agar unsupported by any solid structure—a defining trait of cancer cells. They called the mysterious substance sarcoma growth factor. One fraction of sarcoma growth factor proved responsible for this anchorage-independent growth. Called TGF-β, it was purified in 1981 by Anita Roberts, Ph.D., in the NCI lab of Mike Sporn, M.D., and by Harold Moses, M.D. , then at the Mayo Clinic in Rochester, Minn. In 1980 Todaro and Sporn speculated that tumor cells manufacture their own proteins such as TGF-β in order to grow—the autocrine secretion hypothesis—and that specific inhibitors might control such cancer cells.