Scientists Devise a Protein Switch That Trigger Cancer Cells to Self Medicate

The damaging impact of chemotherapy on healthy cells can now be combated using a protein switch that initiates cancer cells to produce their own anti-cancer medication.

Lab tests conducted by researchers at Johns Hopkins have shown that the protein switches act from within the cells by activating a powerful cell-killing drug when the device detects a marker linked to cancer.

The goal, the scientists said, is to deploy a new type of weapon that causes cancer cells to self-destruct while sparing healthy tissue.

The study reported in the online early edition of Proceedings of the National Academy of Sciences, notes that the new cancer-fighting strategy is an innovative step in treating and initiating cancer therapy.

According to researchers, the impact of the protein switches have yet to be tested on human patients, and much more testing needs to be done to validate current findings.

Chemotherapy is the primary weapon used by oncologists to fight cancer which also damages healthy cells. In the protein switch strategy, researchers suggest that the doctor could administer a prodrug, or an inactive form of a cancer-fighting drug.The cellular protein switch could be triggered only if a cancer marker is present at the cellular level. The switch could then 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 bio molecular engineering professor in the Whiting School of Engineering, who supervised development of the switch.

The healthy cells will also receive the prodrug, he added, 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.

To demonstrate that these switches can work, the research team successfully tested them on human colon cancer and breast cancer cells in Ostermeier's lab and in the laboratory of James R. Eshleman, a professor of pathology and oncology in the Johns Hopkins School of Medicine.

Ostermeier's team fused together two different proteins. One protein was programmed to detect a marker that is produced by cancer cells alone. The other protein, from yeast, could 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 said.

Ostermeier explained that for the protein switch to work, it must first gain entry into the cancer cells. One technique to achieve this could be to enable the switch gene to be delivered inside the cell. The switch gene serves as the blueprint from which the cells' own machinery constructs the protein switch.

Another approach, he said, would be to develop methods to deliver the switch protein itself to cells. Once the switches are in place, the patient would receive the inactive chemotherapy drug, which would turn into a cancer attacker inside the cells where the switch has been turned on.

Despite researchers developing methods to deliver anti-cancer drugs specifically to cancer cells, Ostermeier said the protein switch tactic overcomes difficulties encountered in those methods.

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, he said.