Sanford Burnham Prebys Medical Discovery Institute
La Jolla, California
American Association for Cancer Research
Seeking to identify new therapeutic targets in triple negative breast cancer (TNBC).
Laboratory studies are conducted to test a combination approach to block growth of TNBC tumor cells.
These studies could lead to a new therapeutic strategy to improve outcomes for patients with triple negative breast cancer.
Triple negative breast cancer (TNBC) accounts for 15-20 percent of breast cancers and has a higher mortality than other breast cancer subtypes. The poor prognosis of TNBC can be attributed, in part to the lack of effective targeted therapy.
The vast majority of TNBC have a mutation in the tumor suppressor gene, p53. Although p53 mutations are found frequently in TNBC, it is difficult to target p53-deficiency with drugs. However, Dr. Emerling has shown that by knocking down genes that control p53, cancer cell growth can be blocked. Importantly, she also found that deletion of these genes (called PIP4K2A and PIP4K2B) prevents tumor formation in some models. This suggests that targeting PIP4K2A and PIP4K2B, rather than targeting p53 directly, may prevent tumor growth of TNBC with p53 mutations.
The goal of Dr. Emerling’s BCRF/AACR project is to provide proof-of-concept that targeting these genes would be an effective therapy for p53 mutant breast cancers, especially the TNBC subgroup where targeted therapies have not been effective.
Brooke M. Emerling, PhD is an Assistant Professor in Cancer Metabolism and Signaling Networks at Sanford Burnham Prebys Medical Discovery Institute in La Jolla, California. She received her undergraduate degree from the University of California, Santa Cruz and her graduate degree from Northwestern Medical School. Dr. Emerling is an expert is phosphoinositide signaling and was the first to identify a family of ‘druggable’ enzymes whose loss of function results in synthetic lethality with p53 loss. Prior to her discovery of this synthetic lethality, this novel class of phosphoinositide enzymes, the phosphatidylinositol-5-phosphate 4-kinases (PI5P4Ks), were not a focus for oncology research or cancer metabolism. Her current work focuses on determining the role of PI5P4K in p53 deficient cancers, especially the triple negative subgroup where targeted therapies have not been effective.