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 lev el. Four subtypes of this cancer include luminal A and luminal B, basal-like, and Human Epidermal growth factor Recep-tor 2 (HER2)-enriched (without ER expression). SNARE interactions in vesicular transport and neurotrophin signaling and FoxO signaling pathways in glucose metabolism are probably the mechanisms responsible for side effects of Doxorubicin.Ĭonclusion: Following our model validation using the existing experimental data, we recommend our other newly predicted biomarkers and pathways as possible mole-cular mechanisms and side effects underlying the response to Doxorubicin in breast cancer requiring further investigations.īreast cancer is the most common cause of cancer and mortality caused by cancers in women worldwide 1. The apoptosis in-duction, DNA repair, invasion inhibition, metastasis, and DNA replication are sug-gested as critical molecular mechanisms underlying Doxorubicin anti-cancer effect. Besides, SNARE interactions in vesicular transport and neurotrophin signaling were identified as pathways related to the side effects of Doxorubicin. Enrichment analysis also revealed cell cycle, TP53 signaling, Forkhead box O (FoxO) signaling, and viral carcinogenesis as essential pathways in response to this drug. Results: Analyzing the constructed PPI and gene-TF-miRNA regulatory network showed that MCM3, MCM10, and TP53 are key hub-bottlenecks and seed proteins. Network analysis was performed to iden-tify hubs, bottlenecks, clusters, and regulatory motifs to evaluate crucial genes and molecular mechanisms behind the body response to Doxorubicin and its side effects. Methods: Omics data were extracted and analyzed to construct the protein-protein interaction and gene regulatory networks. We used systems biology and bio-informatics methods to identify essential genes and molecular mechanisms behind the body response to Doxorubicin and its side effects in breast cancer patients. Never-theless, the molecular mechanisms underlying the response to Doxorubicin and its side effects are not comprehensively understood so far. Doxorubicin is an anthracycline used to treat breast cancer as the first treatment choice. Student Research Committee, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranĬellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iranĭepartment of Animal Science, Agriculture and Natural Resources University of Khuzestan, Ahvaz, Iranĭepartment of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran, of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iranīackground: Breast cancer is the most common malignancy worldwide. ![]() Volume 14, Issue 2, April-June 2022, Page
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