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Published on: November 1, 2017
Identification of Potential Molecular Targets of Doxorubicin for Application in Skin Cancer: A Network Pharmacology
Sonali Karhana1, Sanjula Baboota2, Mohd Ashif Khan1
1Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India.
Abstract:
The primary objective was to find the pharmacological targets of doxorubicin and their mechanisms of action, with a dual focus on their therapeutic relevance in skin cancer treatment and their potential involvement in resistance to doxorubicin in cancer cells. The targets of skin cancer and potential targets of doxorubicin were searched from multiple databases. Common targets were chosen using the GeneVenn tool and then imported into the STRING database to construct a protein-protein interaction network. Topological factors were evaluated with Cytoscape to identify core targets. FunRich was used to identify the signaling pathways, molecular functions, cellular components, and biological processes involving the top targets. Molecular docking was conducted using the Molecular Operating Environment software. The top five target genes identified as therapeutic targets of doxorubicin for treatment of skin cancer are poly(ADP-ribose) polymerase, epidermal growth factor receptors, heat shock protein 90 alpha family class A member 1, Harvey rat sarcoma viral oncogene homolog, and mammalian target of rapamycin. In addition, doxorubicin-induced resistance mechanisms were also predicted. Further research on innovative methods of delivering doxorubicin to maximize its effectiveness in treating skin cancer and to prevent the development of resistance to the drug is necessary.
Insights
This study identifies key pharmacological targets of doxorubicin for skin cancer treatment, including PARP and EGFR. It also predicts mechanisms of doxorubicin resistance, highlighting the need for improved drug delivery strategies.
Area of Science:
- Oncology
- Pharmacology
- Bioinformatics
Background:
- Doxorubicin is a crucial chemotherapy agent, but its efficacy in skin cancer is limited by resistance.
- Understanding doxorubicin's precise targets and resistance mechanisms is vital for optimizing treatment.
Purpose of the Study:
- To identify pharmacological targets of doxorubicin in skin cancer.
- To elucidate mechanisms of doxorubicin resistance.
- To explore therapeutic strategies for enhancing doxorubicin effectiveness.
Main Methods:
- Database searches and bioinformatics tools (GeneVenn, STRING, Cytoscape) were used to identify and analyze doxorubicin targets.
- Protein-protein interaction networks and topological analyses pinpointed core targets.
- Molecular docking assessed drug-target interactions.
Main Results:
- Five key therapeutic targets for doxorubicin in skin cancer were identified: poly(ADP-ribose) polymerase (PARP), epidermal growth factor receptors (EGFR), heat shock protein 90 alpha family class A member 1 (HSP90AA1), Harvey rat sarcoma viral oncogene homolog (HRAS), and mammalian target of rapamycin (mTOR).
- Potential mechanisms underlying doxorubicin resistance were predicted.
- Signaling pathways, molecular functions, and biological processes associated with these targets were elucidated.
Conclusions:
- The identified targets (PARP, EGFR, HSP90AA1, HRAS, mTOR) represent promising avenues for doxorubicin-based skin cancer therapy.
- Further investigation into novel drug delivery methods is essential to overcome doxorubicin resistance and improve treatment outcomes.
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