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

Lung cancer triggers pulmonary hypertension

November 17, 2017
Shortness of breath and respiratory distress often increase the suffering of advanced-stage lung cancer patients. These symptoms can be triggered by pulmonary hypertension, as scientists at the Max Planck Institute for Heart ...

Researchers discover an Achilles heel in a lethal leukemia

November 16, 2017
Researchers have discovered how a linkage between two proteins in acute myeloid leukemia enables cancer cells to resist chemotherapy and showed that disrupting the linkage could render the cells vulnerable to treatment. St. ...

Computer program finds new uses for old drugs

November 16, 2017
Researchers at the Case Comprehensive Cancer Center at Case Western Reserve University School of Medicine have developed a computer program to find new indications for old drugs. The computer program, called DrugPredict, ...

Pharmacoscopy improves therapy for relapsed blood cancer in a first clinical trial

November 16, 2017
Researchers at CeMM and the Medical University of Vienna presented a preliminary report in The Lancet Hematology on the clinical impact of an integrated ex vivo approach called pharmacoscopy. The procedures measure single-cell ...

Wider sampling of tumor tissues may guide drug choice, improve outcomes

November 15, 2017
A new study focused on describing genetic variations within a primary tumor, differences between the primary and a metastatic branch of that tumor, and additional diversity found in tumor DNA in the blood stream could help ...

A new strategy for prevention of liver cancer development

November 14, 2017
Primary liver cancer is now the second leading cause of cancer-related death worldwide, and its incidences and mortality are increasing rapidly in the United Stated. In late stages of the malignancy, there are no effective ...

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.