## 3 Results
### Systematic Repositioning of Drugs/Molecules  
Drug discovery is a time-consuming and labor-intensive work process. On average, the development of a new drug takes 10-15 years. Drug repositioning, namely, the use of old drugs for new diseases, is an efficient strategy for its low-cost and riskless characteristics [15]. Several studies have performed systematic approaches, using a combination of in silico and experimental methods, to reposition known drugs/molecules. Table 1 presents the works in the last five years that have implemented in silico and in vitro models for drug discovery using a systematic repositioning of drugs for metastatic BC. In particular, the study of [PERSON] et al. [18] focused on the similarity between the side effects of two different drugs. Indeed, the assumption of the study was that if the two drugs have common side effects, then they can also have common gene targets and clinical indications. In vitro cell line and molecular docking studies have shown that ropinirole shares many side effects with letrozole (used in the management of advanced and metastatic BC) and is efficient in the treatment of breast cancer. An in vitro study of ropinirole on MCF-7 cells by a 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolzolium bromide assay (MTT) was performed to test the ability of ropinirole to inhibit cell growth. Molecular docking showed a good interaction with a good binding affinity of \(-7.8\) kcal/mol between ropinirole and aromatase, a well-known target of letrozole. The three-dimensional structure of aromatase (Protein Data Bank (PDB) ID: 3 EQM) is available for computational docking analysis in the Protein Data Bank (PDB). In a recent study, [PERSON] et al. screened more than 1000 known small molecular compounds and focused on 15 compounds [19], studying their effect on breast cancer cell viability and migration with in vitro studies on MCF-7, MDA-MB-231, and BT-474 BC cell lines. Molecular docking was performed to demonstrate the ability of the binding of the 15 compounds with chemokine ligand 18 (CCL18), as previous studies suggested that CCL18 is a chemokine derived from tumor-associated macrophages (TAMs) to induce BC metastasis [20]. Therefore, CCL18 is considered a potential drug target (PDB ID: 4 MHE). Narrowing the selection of ligands from more than 1000 compounds to 15 was performed by evaluating the binding energy with CCL18 obtained via molecular docking studies. In this way, 15 compounds were selected as potential drugs targeting CCL18, and the toxicity of these 15 compounds was evaluated by using cell counting kit-8 (CCK-8) assays, which indicated that most of the compounds did not influence cell viability. A total of 6 of the 15 compounds inhibited CCL18-induced cell migration; this anticancer activity was also confirmed by adherence and invasion assays [19]. In vitro, in silico, in vivo, and ex vivo analyses have been performed to evaluate the cytotoxic action of etoposide (ET), doxorubicin (DOX), pifithrin-\(\alpha\) (PIF), and dexamethasone (DEX) in triple-negative BC (TNBC) [21]. TNBC is a molecular subtype of BC that is negative for three hormone receptors--namely, estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal receptor 2 (HER2) [21]. ET, a podophyllotoxin derivative, is a chemotherapy medication used against a wide range of cancers (e.g., lung cancer, lymphoma, lung cancer, leukemia, and glioblastoma multiforme), but its efficacy against TNBC is still unknown [22]. DOX, alone or in combination with other drugs, is an effective therapy for numerous cancers, including breast cancer [23]. The antiapoptotic and non-topoisomerase inhibitors PIF and DEX were considered in a previous study as a negative control [21]. In this study, the authors identified tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and death receptor 5 (DR5) as potential drug targets (PDB ID: 4N90) [21]. Molecular docking and molecular dynamics studies have shown the ability of ET, DOX, PIF, and DEX to stabilize the TRAIL-DR5 complex.