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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
siRNA and targeted delivery systems in breast cancer therapy
Sepideh Mirzaei1,2, Mahshid Deldar Abad Paskeh2,3, Maliheh Entezari2,3
1Department of Biology, Faculty of Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Abstract:
Recently, nucleic acid drugs have been considered as promising candidates in treatment of various diseases, especially cancer. Because of developing resistance to conventional chemotherapy, use of genetic tools in cancer therapy appears inevitable. siRNA is a RNAi tool with capacity of suppressing target gene. Owing to overexpression of oncogenic factors in cancer, siRNA can be used for suppressing those pathways. This review emphasizes the function of siRNA in treatment of breast tumor. The anti-apoptotic-related genes including Bcl-2, Bcl-xL and survivin can be down-regulated by siRNA in triggering cell death in breast cancer. STAT3, STAT8, Notch1, E2F3 and NF-κB are among the factors with overexpression in breast cancer that their silencing by siRNA paves the way for impairing tumor proliferation and invasion. The oncogenic mechanisms in drug resistance development in breast tumor such as lncRNAs can be suppressed by siRNA. Furthermore, siRNA reducing P-gp activity can increase drug internalization in tumor cells. Because of siRNA degradation at bloodstream and low accumulation at tumor site, nanoplatforms have been employed for siRNA delivery to suppress breast tumor progression via improving siRNA efficacy in gene silencing. Development of biocompatible and efficient nanostructures for siRNA delivery can make milestone progress in alleviation of breast cancer patients.
Insights
Small interfering RNA (siRNA) offers a novel approach to cancer therapy by silencing oncogenes and overcoming drug resistance in breast tumors. Nanoparticle delivery systems enhance siRNA efficacy for improved breast cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Nucleic acid drugs, particularly siRNA, are emerging as potent therapeutic agents for cancer treatment.
- Developing resistance to conventional chemotherapy necessitates the exploration of genetic tools like siRNA for cancer therapy.
- siRNA targets and suppresses specific genes, offering a precise approach to combat cancer.
Purpose of the Study:
- This review focuses on the application of siRNA in treating breast cancer.
- To highlight siRNA's role in down-regulating key oncogenic factors and pathways involved in breast tumor progression.
- To discuss the potential of siRNA in overcoming drug resistance mechanisms in breast cancer.
Main Methods:
- Review of existing literature on siRNA therapy for breast cancer.
- Analysis of siRNA's mechanism in targeting anti-apoptotic genes (Bcl-2, Bcl-xL, survivin).
- Examination of siRNA's role in silencing proliferation and invasion-related factors (STAT3, STAT8, Notch1, E2F3, NF-κB).
- Investigation of siRNA's impact on drug resistance mechanisms, including lncRNAs and P-gp activity.
- Evaluation of nanoplatforms for enhanced siRNA delivery and tumor accumulation.
Main Results:
- siRNA effectively down-regulates anti-apoptotic genes, promoting cell death in breast cancer.
- Silencing of oncogenic factors like STAT3, STAT8, Notch1, E2F3, and NF-κB by siRNA inhibits tumor proliferation and invasion.
- siRNA can suppress lncRNAs, crucial in developing breast tumor drug resistance.
- siRNA reduces P-gp activity, enhancing drug uptake in tumor cells.
- Nanoplatforms improve siRNA delivery, stability, and tumor accumulation, boosting therapeutic efficacy.
Conclusions:
- siRNA demonstrates significant potential as a therapeutic agent for breast cancer by targeting critical oncogenic pathways and overcoming resistance.
- The development of advanced nanostructures for siRNA delivery is crucial for improving treatment outcomes and patient prognosis in breast cancer.
- siRNA-based therapies, particularly when delivered via nanoplatforms, represent a promising frontier in the fight against breast cancer.
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