New drug holds promise for GIST"s sister cancer

LOS ANGELES (Newswise) — An experimental therapy that may battle resistance to the drug Gleevec in patients with chronic myeloid leukemia (CML) has shown promising results in a study at UCLA’s Jonsson Cancer center, increasing survival in animal models and perhaps paving the way for a second generation targeted therapy.

The results of the study appear in the July 16 issue of the peer-reviewed journal Science, published by the American Association for the Advancement of Science. Early phase human studies of BMS354825, being developed by Bristol-Myers Squibb, already are underway at the Jonsson Cancer Center in CML patients who developed a resistance to Gleevec.

About 15 to 20 percent of CML patients who take Gleevec become resistant to the drug and suffer a relapse, leaving them with few effective treatment options, said Dr. Neil Shah, an oncologist and researcher, an assistant professor of hematology/oncology and the study’s first author. In patients with resistant disease, secondary mutations in the gene linked to CML allow the cancer to evade therapy. It is those mutations that are targeted by the BMS354825, which is taken in pill form like Gleevec.

“Learning from what happens when a drug fails in some patients can lead to a new treatment paradigm,” Shah said. “In the future, we may be combining therapies that can, amongst them, override all the resistance mechanisms that allow cancer to evade individual therapies. In the future, cancer may be treated similarly to HIV, with a cocktail of drugs.”

Shah said the drug also may be useful for treating other diseases that respond to Gleevec initially, such as gastrointestinal stromal tumors.

Gleevec is a tyrosine kinase inhibitor, a new class of drugs that can interfere with cell signaling pathways implicated in tumor development.

Dr. Charles Sawyers, a professor of hematology/oncology, an investigator with the Howard Hughes Medical Institute and the senior author of the study, said this work could represent a major advance for the patients who suffer a relapse on Gleevec.

“Gleevec remains a spectacular step forward in the application of targeted therapy to CML specifically, and serves as a model for how to do this more generally in cancer,” Sawyers said. His paper reports the effectiveness of the BMS inhibitor in Gleevecresistant cells in tissue culture and in mice. If the experimental inhibitor proves effective in human patients as well, future studies may eventually pair Gleevec with BMS354825.

“We hope this represents another viable treatment option for patients with this disease,” Shah said. “There may now be hope beyond Gleevec should their disease relapse.”