Charles Perou, PhD, Professor of Genetics and Pathology and Laboratory Medicine and the May Goldman Shaw Distinguished Professor of Molecular Oncology was corresponding author of a study that focused on finding possible drug targets in triple-negative breast cancers.
The paper, titled “Genomic Profiling of Murine Mammary Tumors Identifies Potential Personalized Drug Targets for p53-Deficient Mammary Cancers” was published in the 01 July 2016 issue of Disease Models and Mechanisms. Along with colleagues from Washington University, University of Albany and Baylor College of Medicine, the Perou laboratory utilized a murine Trp53-null mammary transplant tumor model to identify additional drivers and possible drug targets of the triple-negative breast cancer phenotype. Two subsets of transplant tumors resembled human basal-like subtype and DNA-microarray, whole-genome and exome-based sequencing were used to study the secondary genetic aberrations which were compared to human basal-like tumors to identify conserved somatic genetic features. After filtering the candidates (gene deemed essential in at least 5% of human breast cancer cell lines), five potential personalized drug target genes were identified, including Cul4a, Lamp1, Met, Pnpla6 and Tubgcp3. Inhibition of Met using crizotinib caused Met-amplified murine tumors to undergo complete regression, identifying Met as a promising drug target in the mouse tumor models and highlighting the utility of comparative genomic studies and preclinical models for interrogating tumor signaling pathways.
Link to the article: http://www.ncbi.nlm.nih.gov/pubmed/27149990