We've previously looked at the development of cancer treatments that deliver drugs directly into cancer cells before releasing their chemotherapeutic payload to reduce the damage done to healthy cells. But a new protein "switch" approach developed by researchers at Johns Hopkins University changes the game again by instructing cancer cells to produce their own cancer medication and cause the cancer cells to self-destruct while sparing healthy tissue.
The protein switch strategy would see a doctor administering a "prodrug," which is an inactive form of a cancer-fighting drug that would only be activated when it detects the presence of a cancer marker, triggering the cellular switch to turn the harmless prodrug into a potent form of chemotherapy.
"The switch in effect turns the cancer cell into a factory for producing the anti-cancer drug inside the cancer cell," said Marc Ostermeier, a Johns Hopkins chemical and biomolecular engineering professor in the Whiting School of Engineering, who supervised development of the switch. "The healthy cells will also receive the prodrug and ideally it will remain in its non-toxic form. Our hope is that this strategy will kill more cancer cells while decreasing the unfortunate side effects on healthy cells."
The research team made the cancer-fighting switch by fusing together two different proteins; one that detects a marker that cancer cells produce and another protein extracted from yeast that can turn an inactive prodrug into a cancer-cell killer.
"When the first part of the switch detects cancer, it tells its partner to activate the chemotherapy drug, destroying the cell," Ostermeier explained.
For the technique to work, the switch first needs to get inside the cancer cells. Ostermeier says this can be done in one of two ways; by delivering the switch protein itself into the cells or, alternatively, delivering the switch gene inside the cell where it serves as the blueprint from which the cell's own machinery constructs the protein switch.
Once the switches are in place, the patient would receive the inactive chemotherapy drug, which would then be activated inside the cells where the switch has been flipped on.
"The protein switch concept changes the game by providing a mechanism to target production of the anti-cancer drugs inside cancer cells instead of targeting delivery of the anti-cancer drug to cancer cells," Ostermeier said.
Although the novel cancer-fighting strategy hasn't yet been tested on human patients, the research team has successfully tested the switches on human colon cancer and breast cancer cells in the lab. The next step is animal testing, which is expected to begin within a year.
"This is a radically different tool to attack cancers," said James R. Eshleman, a professor of pathology and oncology in the Johns Hopkins School of Medicine and a co-author of the paper that appears in the Proceedings of the National Academy of Sciences, "but many experiments need to be done before we will be able to use it in patients."
