Rapamycin isn't your ordinary potential anti-cancer drug…It had a long and somewhat exotic history before undergoing preclinical (laboratory-based) studies at St. Jude as part of a national Pediatric Preclinical Testing Program (PPTP) investigation of its anticancer activity.
Scientists originally discovered that bacteria in a soil sample from the isolated triangle of volcanic rock in the South Pacific known as Easter Island produced rapamycin, and that it was a good anti-fungal agent.
But when drug makers discovered it also could prevent rejection of transplanted organs by suppressing the immune system, rapamycin’s career took a significant turn. And still later, scientists discovered it had anti-cancer activity as well.
Rapamycin is a highly specific inhibitor of the molecule mTOR, an enzyme the cell needs to turn genetic blueprints into specific proteins required for cell growth.
When used to treat cancer, such highly specific drugs are called molecularly targeted therapy; they are designed to inhibit specific molecules rather than “poison” the cell as a whole. This strategy, which depends on discovering precise protein targets, is likely to reduce the level of toxic side effects common with standard chemotherapy, according to Peter Houghton, PhD, Molecular Pharmacology chair.
In a report appearing in the online edition of Pediatric Blood Cancer, an international team of PPTP investigators led by Houghton describes results of a series of laboratory tests that put rapamycin through its anti-cancer paces.
PPTP is a consortium of institutions in the United States and Australia that tests agents or combinations of agents in laboratory cultures and mouse models of common childhood cancers. The program is supported through a National Cancer Institute research contract, with Houghton as the principal St. Jude investigator.
The current study was a stage I (preclinical) PPTP investigation of rapamycin’s ability to inhibit growth of specific cancers, either in culture dishes or in mouse models of the cancers. The team reported that rapamycin is effective in tumor cultures and mouse models of diseases such as the solid tumors rhabdomyosarcoma and osteosarcoma, as well as in acute lymphoblastic leukemia.