Figure 4

Coexpression subnetworks for each of the Pareto optimal genes. (a) Coexpression partners of CYB5R3, MYLK, EPCAM, BMP2, and PAFAH1B3, prior to letrozole treatment. (b) Following letrozole treatment, the number and identity of coexpression partners of these genes changed, illustrating the context-dependent nature of gene–gene associations and suggesting that these genes may have an important role in maintaining the tumor phenotype in an estrogen-depleted environment. Targeting one or more of these genes sequentially following letrozole treatment, after the tumors have adapted to the drug, may have a synergistic effect resulting in further reductions in tumor volume.