Drug kills cancer cells by restoring faulty tumor suppressor

May 14, 2012

A new study describes a compound that selectively kills cancer cells by restoring the structure and function of one of the most commonly mutated proteins in human cancer, the "tumor suppressor" p53. The research, published by Cell Press in the May 15th issue of the journal Cancer Cell, uses a novel, computer based strategy to identify potential anti-cancer drugs, including one that targets the third most common p53 mutation in human cancer, p53-R175H. The number of new cancer patients harboring this mutation in the United States who would potentially benefit from this drug is estimated to be 30,000 annually.

P53 recognizes cellular stress and either puts the brakes on , or kills the cell if the damage is irreparable. The gene encoding p53 is mutated in over half of human cancers, and loss of p53 function has been linked to many aspects of cancer including aggressiveness, metastasis and poor response to chemotherapy and radiation. "Restoring the function of mutant p53 with a drug has long been recognized as an attractive cancer therapeutic strategy," explains senior study author, Dr. Darren R. Carpizo, from The Cancer Institute of New Jersey. "However, it has proven difficult to find compounds that restore the lost function of a defective tumor-suppressor."

Dr. Alexei Vazquez, a co-author of the study, developed a computer based screening method to identify compounds that target tumor cells with , but not cells with normal p53. The screening method was unique because it involved with diverse , a model that recapitulates what is seen in actual human cancers. This method identified several compounds that killed cancer cells containing mutant p53. One of the compounds did so by restoring the structure and function of the p53-R175H mutant. The researchers went on describe the details of the reactivation mechanism and showed that normal cells were not impacted by the compound.

In addition to identifying a compound for selectively restoring the function of the p53-R175H mutant, the findings also support the development of rationally targeted cancer therapies. "Anti-cancer drug development is moving in the direction of "personalized medicine" in which the drugs are chosen based on the molecular pathways that are deranged in an individual patient's tumor," concludes Dr. Carpizo. "Our findings support the growing trend in developmental therapeutics in which the efficacy of future will depend upon the knowledge of the patient's tumor genotype."

Explore further: New drug shrinks cancer in animals, study shows

More information: Yu et al.: "Allele Specific p53 Mutant Reactivation." DOI:10.1016/j.ccr.2012.03.042

Related Stories

New drug shrinks cancer in animals, study shows

April 6, 2011
A study led by researchers at the University of Michigan Comprehensive Cancer Center showed in animal studies that new cancer drug compounds they developed shrank tumors, with few side effects.

Why cholesterol-lowering statins might treat cancer

January 19, 2012
Cholesterol-lowering statins seem to keep breast cancer at bay in some patients. Now researchers reporting in the January 20th issue of the journal Cell, a Cell Press publication, provide clues about how statins might yield ...

Recommended for you

Researchers release first draft of a genome-wide cancer 'dependency map'

July 27, 2017
In one of the largest efforts to build a comprehensive catalog of genetic vulnerabilities in cancer, researchers from the Broad Institute of MIT and Harvard and Dana-Farber Cancer Institute have identified more than 760 genes ...

Cancer-death button gets jammed by gut bacterium

July 27, 2017
Researchers at Michigan Medicine and in China showed that a type of bacterium is associated with the recurrence of colorectal cancer and poor outcomes. They found that Fusobacterium nucleatum in the gut can stop chemotherapy ...

Long-sought mechanism of metastasis is discovered in pancreatic cancer

July 27, 2017
Cells, just like people, have memories. They retain molecular markers that at the beginning of their existence helped guide their development. Cells that become cancerous may be making use of these early memories to power ...

Blocking the back-door that cancer cells use to escape death by radiotherapy

July 27, 2017
A natural healing mechanism of the body may be reducing the efficiency of radiotherapy in breast cancer patients, according to a new study.

Manmade peptides reduce breast cancer's spread

July 27, 2017
Manmade peptides that directly disrupt the inner workings of a gene known to support cancer's spread significantly reduce metastasis in a mouse model of breast cancer, scientists say.

Glowing tumor technology helps surgeons remove hidden cancer cells

July 27, 2017
Surgeons were able to identify and remove a greater number of cancerous nodules from lung cancer patients when combining intraoperative molecular imaging (IMI) - through the use of a contrast agent that makes tumor cells ...

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.