Researchers say decoy shows promise as cancer-fighter in novel phase 0 trial

August 13, 2012

(Medical Xpress) -- A critical protein that had been deemed “undruggable” can be effectively targeted by using a decoy to fool the body into a cancer-fighting response, according to researchers at the University of Pittsburgh Cancer Institute (UPCI) and the University of Pittsburgh School of Medicine. In a report in the August issue of Cancer Discovery, they showed the decoy was successful in a phase 0 study, an uncommon but useful preface to the commencement of standard human trials.

Activation and increased signaling of a protein known as Signal Transducer and Activator of Transcription 3 (STAT3) has been identified in many cancers and is associated with poor prognosis, said senior author Jennifer Grandis, M.D., professor of otolaryngology and pharmacology and chemical biology, Pitt School of Medicine, and director of the Head and Neck Program at the University of Pittsburgh Institute (UPCI). Transcription factors such as STAT3 regulate the activity, or expression, of other genes; in adult tissues, STAT3 triggers the production of other proteins that promote the growth and survival of cancer cells.

“Lab experiments have shown that inhibiting STAT3 activity or function limits the proliferation and survival of a variety of cancer cell lines,” she explained. “But the drugs that have been tested in patients are not selective for STAT3 and haven’t been effective.”

So her research team tried an unusual approach: they fooled the STAT3 protein into binding to a harmless decoy that they engineered, rather than the real gene sequence that would have initiated the production of cancer-promoting proteins. Preclinical experiments showed that the strategy was tolerated well and didn’t produce toxic side effects.

To further justify clinical development, the team conducted a phase 0 study to see if the decoy would work in humans. First, they took biopsies of head and neck cancers in 30 patients who were having surgery to remove the tumors. At the start of the operation, the tumors were injected with either the decoy or a salt-water placebo. After surgery, about four hours after injection, the cancerous tissue that had been taken out of each patient was biopsied again. Tests were conducted in the specimens to determine the activity of genes regulated by STAT3.

“We found reduced expression of the STAT3 target genes in tumors that had been treated with the decoy compared to those that got a placebo injection and to pre-treatment samples,” Dr. Grandis said. “This indicates we were able to selectively inhibit STAT3, which is a significant step forward.”

The researchers also developed a version of the decoy that could be injected into the bloodstream, which inhibited tumor growth in a mouse model of head and neck cancer.

Explore further: New drug target for kidney disease discovered

Related Stories

New drug target for kidney disease discovered

April 26, 2011
Two discoveries at UC Santa Barbara point to potential new drug therapies for patients with kidney disease. The findings are published in this week's issue of the Proceedings of the National Academy of Sciences.

Curcumin compound improves effectiveness of head and neck cancer treatment

May 19, 2011
A primary reason that head and neck cancer treatments fail is the tumor cells become resistant to chemotherapy drugs. Now, researchers at the University of Michigan Comprehensive Cancer Center have found that a compound derived ...

Combination drug therapy urged to battle lung cancer

February 2, 2012
Combination drug therapy may be needed to combat non-small cell lung cancer (NSCLC), according to a study by the Translational Genomics Research Institute (TGen) and Van Andel Research Institute (VARI).

New study finds compounds show promise in blocking STAT3 signaling as treatment for osteosarcoma

April 11, 2011
A study appearing in the journal Investigational New Drugs and conducted by researchers at Nationwide Children's Hospital, discovered that two new small molecule inhibitors are showing promise in blocking STAT3, a protein ...

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

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.