Keck School of Medicine of USC scientists have discovered that a protein commonly over-expressed in solid cancerous cells – one previously found to enable breast, prostate and other tumors to grow and resist treatment – also is over-expressed in multiple types of leukemia and can be successfully targeted to block the disease.
“Our work shows that if you suppress the level of the protein GRP78 in human leukemic cells, these cells are killed more efficiently by chemotherapy,” said Amy Lee, professor of biochemistry and molecular biology at the Keck School and associate director for basic research at the USC Norris Comprehensive Cancer Center, who served as principal investigator of the study. “We discovered that GRP78 is necessary for the activation of the P13K/AKT signaling pathway, a major pathway that helps leukemia cells to survive, proliferate and become drug resistant.”
The findings were published in the journal Blood, a highly regarded hematology publication. The research, which used mice models to study leukemia development and human leukemia cells to examine responsiveness to drug therapy, was funded by the National Cancer Institute.
Lee said that drug design is under way to inactivate GRP78.
“This novel approach to block the P13K/AKT pathway could have great clinical implications for a wide range of cancers and may avoid complications that accompany other types of therapy,” she said.
Joining Lee in the study were co-authors and graduate students Shiuan Wey and Biquan Luo, research assistant Chun-Chih Tzeng and collaborators at New York University.
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