UIC research suggests new way to stop growth of cancer cells

November 11, 2002

A new study from the UIC College of Pharmacy may lead to the development of a drug to stop the growth of cancer cells. The study, published in the September issue of the journal Nature Medicine, was described in an editorial in the journal Nature as being among the most important recent findings in cancer-targeting research.

Dr. Lucio Miele, associate professor of biopharmaceutical sciences, and his team have developed a gene therapy approach as well as a potentially new use for a class of drugs known as GSIs, or gamma-secretase inhibitors, which are already under investigation as a treatment for Alzheimer's disease.

GSIs are drugs that block gamma secretase, an enzyme that produces a harmful protein in the brains of people with Alzheimer's. Miele's study shows that inhibiting gamma secretase also can block intercellular communications in cancer cells.

Cancer occurs when several genes within a cell are damaged. Earlier research has found that a type of gene called Ras is one of the most commonly damaged or inappropriately activated genes in human malignant tumors. Miele's research builds on that discovery.

His findings show that when damaged or excessively activated in human cells, Ras, through gamma secretase, activates a protein known as Notch-1, which in turn triggers a chain of events that allow cancer cells to grow.

"If we stop Notch, we stop Ras and, ultimately, we can stop cancers that depend on it for survival," Miele says.

Miele is one of several scientists who have been finding Notch gene alterations in various cancers. "But all that had been found so far was that the expression of these genes seemed increased in various tumors for unknown reasons," Miele said. "Nobody had described what causes this alteration, nor, most importantly, that these genes and proteins can be directly targeted for cancer treatment.

"The really exciting discovery for us is that you can stop cancer cells by just switching off these Notch genes or blocking the activation of notch proteins by gamma secretase," he said.

"This therapy works very well in model human cancer cells created in the laboratory, and it works even better in cells from an actual cervical cancer," Miele said, noting that this result was demonstrated both in the test tube and in experimental tumors formed by human cancer cells in mice. The test tube and mouse studies indicate that gamma secretase inhibitors warrant further investigation, he says. "This means there is a new potential target against which cancer drugs can be developed."

While Miele cautions that more studies are needed to establish which types of cancer could benefit from gamma secretase-blocking drugs or Notch-blocking gene therapy, he says his research and work from other laboratories indicate the potential for therapeutic applications to several types of human malignancies, including breast, cervical, head and neck, endometrial and renal cancers, some colon and lung cancers, aggressive melanomas, pleural mesotheliomas and certain lymphomas and leukemias.

Miele, a member of the UIC Cancer Center, expects to begin preliminary testing next year that may eventually lead to human clinical trials.

For more information about the UIC Cancer Center, visit www.uic.edu/com/cancer/.

University of Illinois at Chicago

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