Protein 'switches' could turn cancer cells into tiny chemotherapy factories

September 23, 2011

Johns Hopkins researchers have devised a protein "switch" that instructs cancer cells to produce their own anti-cancer medication.

In lab tests, the researchers showed that these switches, working from inside the cells, can activate 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.

This new cancer-fighting strategy and promising early lab test results were reported this week in the online early edition of . Although the switches have not yet been tested on human patients, and much more testing must be done, the researchers say they have taken a positive first step toward adding a novel weapon to the difficult task of treating cancer.

One key problem in fighting cancer is that broadly applied chemotherapy usually also harms healthy cells. In the protein switch strategy, however, a doctor would instead administer a "prodrug," meaning an inactive form of a cancer-fighting drug. Only when a is present would the cellular switch turn this 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," 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 and 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.

"This is a radically different tool to attack cancers," said Eshleman, a co-author of the PNAS journal article, "but many experiments need to be done before we will be able to use it in patients."

The next step is animal testing, expected to begin within a year, Ostermeier said.

Ostermeier's team made the cancer-fighting switch by fusing together two different proteins. One protein detects a marker that cancer cells produce. The other protein, from yeast, 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 said.

In order for this switch to work, it must first get inside the cancer cells. Ostermeier said this can be done through a technique in which the switch gene is delivered inside the cell. The switch gene serves as the blueprint from which the cell's 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 flipped on.

Although many researchers are developing methods to deliver anti-cancer drugs specifically to cancer cells, Ostermeier said the protein switch tactic skirts difficulties encountered in those methods.

"The protein 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 ," he said.

More information: The paper, "A protein therapeutic modality founded on molecular recognition," can be viewed online at: www.pnas.org/content/early/201 … 803108.full.pdf+html

Related Stories

Recommended for you

Study prompts new ideas on cancers' origins

December 16, 2017
Rapidly dividing, yet aberrant stem cells are a major source of cancer. But a new study suggests that mature cells also play a key role in initiating cancer—a finding that could upend the way scientists think about the ...

What does hair loss have to teach us about cancer metastasis?

December 15, 2017
Understanding how cancer cells are able to metastasize—migrate from the primary tumor to distant sites in the body—and developing therapies to inhibit this process are the focus of many laboratories around the country. ...

Cancer immunotherapy may work better in patients with specific genes

December 15, 2017
Cancer cells arise when DNA is mutated, and these cells should be recognized as "foreign" by the immune system. However, cancer cells have found ways to evade detection by the immune system.

Scientists pinpoint gene to blame for poorer survival rate in early-onset breast cancer patients

December 15, 2017
A new study led by scientists at the University of Southampton has found that inherited variation in a particular gene may be to blame for the lower survival rate of patients diagnosed with early-onset breast cancer.

Scientists unlock structure of mTOR, a key cancer cell signaling protein

December 14, 2017
Researchers in the Sloan Kettering Institute have solved the structure of an important signaling molecule in cancer cells. They used a new technology called cryo-EM to visualize the structure in three dimensions. The detailed ...

'Bet hedging' explains the efficacy of many combination cancer therapies

December 14, 2017
The efficacy of many FDA-approved cancer drug combinations is not due to synergistic interactions between drugs, but rather to a form of "bet hedging," according to a new study published by Harvard Medical School researchers ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.