![]() ![]() Gene regulatory networks contain information about regulatory elements of gene expression. Identifying network modules and their biological functions helps decipher the molecular mechanisms of drug effects, identify new drug targets, predict body response to drugs, and organism behavior 23– 25. Global expression data-based computational approaches can utilize gene interaction information for modeling Protein-Protein Interaction Networks (PPINs) and Gene Regulatory Networks (GRNs). Several network analysis studies of drug-disease associations have been used to predict drug side effects with high accuracy. These networks can help understand how drugs influence the disease at the molecular level and identify the crucial gene sets underlying various drug effects 19– 22. Several such studies rely on network topology analysis to identify the effect of chemotherapy on various cancers. Systems biology and network-based methods are recently used to decipher the molecular mechanisms behind drugs and their possible side effects. Some investigations have even reported cardiotoxic side effects for DXR that their molecular mechanisms remain to be deciphered in detail 18. Nevertheless, little is known about the molecular basis of its effect on cell proliferation, estrogen/estrogen receptor signaling, and cell cycle progression 15– 17. The response rates to DXR in patients exposed to DXR for the first time is reported to be 48%, and for more than once is 28% 14. DXR is among the chemotherapy drugs approved to treat ER+breast cancer. DXR induces Reactive Oxygen Species release (ROS) that ROS lead to DNA damage, lipid peroxidation and membrane damage, and apoptotic cell death pathways 13. This drug is used to treat several cancers, including breast, gastric, lung, ovarian, thyroid, sarcoma, non-Hodgkins and Hodgkins lymphoma, multiple myelo-ma, and pediatric cancers 11, 12. Several studies have shown an adverse effect of ER signaling on motility and invasion of cells 6, 7, while a few studies suggested a positive effect of ER signaling on motility and invasion 8, 9.ĭoxorubicin (DXR) is an anthracycline and chemotherapeutic drug isolated from Streptomyces peucetius 10. In clinical diagnosis, 75% of breast tumors are ER+ 5 however, the role of ER signaling in metastasis of breast cancer remains poorly understood. The ER receptor is one of the therapeutic targets for ER+ breast cancer 4. The dysregulation of the Estrogen Receptor (ER) is attributed to two-thirds of all breast cancers. The estrogen hormone and its receptor play essential roles in breast cancer progression. Breast cancer is often curable early, but the metastatic form is almost mortal due to therapeutic resistance 3. The characterization influence biologically-directed therapies and treatment de-escalation 2. This cancer is a heterogeneous disease at the molecular level. Four subtypes of this cancer include luminal A and luminal B, basal-like, and Human Epidermal growth factor Receptor 2 (HER2)-enriched (without ER expression). Breast cancer is the most common cause of cancer and mortality caused by cancers in women worldwide 1. ![]()
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