Researchers at Childrens Hospital Los Angeles Identify a Novel Mechanism to Overcome Resistance to Targeted Therapy

April 10, 2008

Findings are published in the Journal of the National Cancer Institute

LOS ANGELES - Min H. Kang, PharmD, director of the Leukemia Preclinical Testing Laboratory of the USC-CHLA Institute for Pediatric Clinical Research at Childrens Hospital Los Angeles, and an assistant professor of pediatrics at the Keck School of Medicine of the University of Southern California (USC), has identified a novel mechanism to overcome resistance to targeted therapy.

Dr. Kang’s findings are published in the current issue of the Journal of the National Cancer Institute in an article entitled, “Mechanism of Synergy of N-(4-Hydroxyphenyl) retinamide and ABT-737 in Acute Lymphoblastic Leukemia Cell Lines: Mcl-1 Inactivation.”

Acute Lymphoblastic Anemia (ALL) is the most common childhood cancer with 2,400 newly diagnosed cases each year in the United States. “The purpose of our study is to develop a combination of novel drugs that will improve treatment outcome of childhood ALL by targeting a family of proteins named Bcl-2, that cause drug resistance in leukemia,” Dr. Kang said.

To date, 25 different Bcl-2 family proteins have been identified. Some of these proteins increase cell death, while others inhibit cell death. “By targeting ‘pro-life’ Bcl-2 proteins, we expect to improve the outcome of leukemia treatments,” Dr. Kang said.

ABT-737 is currently being tested in adult cancer patients. “We found that a protein called Mcl-1 is increased in leukemia cells that are resistant to ABT-737 when the cells are treated with the agent,” Dr. Kang said. “We also found that tumor cell resistance to ABT-737 can be overcome by another drug that we are testing, called fenretinide. We have observed that fenretinide inhibits Mcl-1, and the inhibition of Mcl-1 expression is likely to underlie, at least in part, the synergistic cytotoxicity between ABT-737 and 4-HPR in ALL cell lines.”

Dr. Kang received a bachelor’s degree from Chungbuk National University (1990) in South Korea, and a doctorate (1998) from the University of Colorado.

Dr. Kang has authored more than 40 peer-reviewed articles and abstracts.

The USC-CHLA Institute for Pediatric Clinical Research (IPCR), established in 2006 with an anonymous $15 million grant, is one of the most active and productive pediatric clinical trials programs in the nation, conducting research on pediatric illness and disease with a particular emphasis on clinical trials. The IPCR’s programs are designed to find the best means to diagnose, treat and prevent pediatric disease and to promote child and adolescent health.

The IPCR’s Development Therapeutics Program conducts translational and clinical research focused on developing novel therapies to treat catastrophic childhood illness, in particular leukemia and neuroblastoma.