Abstract SY43-03: Screening for triple negative breast cancer vulnerabilities

There is no targeted therapy for triple negative breast cancers (TNBC), which have the worst prognosis of human breast cancers. TNBCs are prone to relapse and metastasize after cytotoxic drug treatment. This group of cancers, defined by low or absent expression of estrogen, progesterone and Her2 receptors, are heterogeneous in genetic, epigenetic and phenotypic features, making it difficult to identify specific drug targets suitable for this group of cancers as a whole. About half or more of TNBCs have an epithelial phenotype (classified based on gene expression profiling as basal-like or basal-A) and a large minority of the remaining tumors are mesenchymal (classified as basal-B). To identify selective genetic dependencies of the basal-like subtype of TNBC that are not required for survival of normal breast epithelial cells, which might be good targets for targeted drug therapy, we first performed a genome-wide siRNA lethality screen that compared two human breast epithelial TNBC cell lines transformed with the same genes in different media - basal-like BPLER and myoepithelial HMLER. BPLER are highly malignant and enriched for tumor-initiating cells, forming tumors in nude mice after injection of just 50 cells, while the more differentiated HMLER cell line only forms tumors when more than 50,000 cells are injected. The screen identified 154 genes on which BPLER, but not HMLER, depended. Expression of the 154 BPLER dependency genes correlated with poor prognosis in breast, bu...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Experimental and Molecular Therapeutics Source Type: research