A Systems Biology Approach to Identify Molecular Determinants of Resistance in Breast Cancer

De novo and acquired resistance to anti-estrogen therapy and aromatase inhibitors remains a challenge in the treatment of estrogen-receptor positive breast cancer. We employed a systems biology approach to identify survival determinants of estrogen independent breast cancer cells with varying sensitivities to hormonal therapeutics. An estrogen receptor-centered network was developed using bioinformatics databases to probe, with a network-targeted 631-element siRNA library, for essential genes involved in the proliferation and survival of estrogen independent breast cancer cells. We identified a unique subset of 25 genes that are essential for the proliferation of estrogen independent breast cancer cells, 15 of which also promote apoptosis.Ph.D., Biomedical Engineering -- Drexel University, 201